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Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with adrenocorticotrophin hormone (ACTH) independent Cushing syndrome (see this term) and is characterized by small to normal sized adrenal glands containing multiple small cortical pigmented nodules (less than 1 cm in diameter).
## Epidemiology
The prevalence of endogenous Cushing syndrome (CS; see this term) is estimated at 1/26,000. PPNAD is responsible for less than 2% of cases. PPNAD is more frequent in females, especially after puberty.
## Clinical description
Although the majority of cases are diagnosed in the 2nd and 3rd decades of life, a substantial proportion of patients present during early childhood (2-3 years). Patients with PPNAD often present with atypical CS, which is characterized by an asthenic, rather than obese, body habitus caused by severe osteoporosis, short stature and severe muscle and skin wasting. Patients with atypical CS have normal or near normal 24-hour urinary free cortisol production, but this is characterized by the absence of the normal circadian rhythmicity of cortisol. In adolescents and children with PPNAD, the disease frequently presents with periodic CS in which normal cortisol production is interrupted by days or weeks of hypercortisolism.
## Etiology
More than 90% of reported cases of PPNAD occur as one of the manifestations of Carney complex (CNC; see this term). Although rare, familial cases of isolated PPNAD have also been reported. The condition is inherited in an autosomal dominant manner and can be associated with mutations in the PRKAR1A, PDE11A and PDE8B genes.
## Diagnostic methods
Diagnosis is first based on confirmation of hypercortisolism (24hr urinary free cortisol, late night salivary cortisol, low-dose and high-dose dexamethasone-suppression test and assessment of midnight plasma cortisol). The second step is plasma ACTH detection to distinguish ACTH-independent CS (values lower than 5-10 pg/ml) from ACTH-dependent CS (see these terms). In some cases, nodules are visible on adrenal gland computed tomography (CT) or magnetic resonance imaging (MRI). The combination of atrophy and nodularity gives the glands an irregular contour, which is distinctly abnormal and diagnostic, especially in younger patients. Patients with PPNAD should also be screened for CNC and its potentially serious components.
## Differential diagnosis
Differential diagnoses are ACTH-dependent CS, including pituitary (Cushing disease) or extra-pituitary tumors (ectopic ACTH secretion) and the other causes of ACTH-independent CS including adrenal adenoma and carcinoma (see these terms).
## Genetic counseling
Genetic testing for mutations of PRKAR1A, PDE11A and PDE8B genes may be discussed to detect affected patients in families with identified mutations. Genetic counseling may be offered in families with these mutations.
## Management and treatment
Bilateral adrenalectomy is the most common treatment for CS due to PPNAD followed by life-long cortisol and mineralocorticoid supplementation.
## Prognosis
Without treatment, CS due to PPNAD can be life-threatening.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Primary pigmented nodular adrenocortical disease | c1864851 | 2,300 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=189439 | 2021-01-23T17:01:28 | {"gard": ["10906"], "mesh": ["C566472"], "omim": ["610475", "610489", "614190", "615830"], "icd-10": ["E24.8"], "synonyms": ["PPNAD", "Primary pigmented nodular adrenal dysplasia"]} |
Breus' mole
Other namesOva tuberculosa,[citation needed] massive mole
SpecialtyObstetrics
Breus' mole is a massive, subchorionic, tuberous hematoma, formed out of maternal blood in the uterus in pregnancy. It was first described by Karl Breus in 1892.[1][2][3]
## Contents
* 1 Cause and pathogenesis
* 2 Diagnosis
* 3 Prognosis
* 4 References
* 5 External links
## Cause and pathogenesis[edit]
It is a rare disease, with an incidence of 1 in 1200 placentas.[4] Women with cardiac problems, disorders of circulation, monosomy, hypertension and diabetes are predisposed to Breus' mole. The mole is formed as a sub-chorionic hematoma, formed out of the intervillous blood, causing progressive accumulation of the clotting substance called fibrin with increasing gestational age. Evidence from Southern blot test reveals that 85 percent of the clotted material is maternal blood. Breus mole is reported to be found in the placetae of macerated stillborn foetuses, indicating that massive subchorionic hematoma could have been the cause of their demise.[5] A massive Breus' mole can cause disturbances in blood flow in the spiral arteries and might result in intrauterine growth restriction of the foetus.
## Diagnosis[edit]
Clinically, Breus' mole may be asymptomatic, or may present with signs of decreased blood flow to the foetus such as growth restriction and foetal distress. Postnatally, Breus' mole is found in placental examination following live birth or spontaneous abortion. Breus' mole is diagnosed antenatally by ultrasound, where a thick multilobulated hematoma can be seen beneath the chorion. Occasionally, subchorial thrombohematoma may later become intraplacental, making its diagnosis difficult. The mole may be echogenic or hypoechoic depending upon the amount of fresh blood present in it.[6] Breus' mole should be differentiated from vesicular mole and missed abortion in an ultrasound examination.
## Prognosis[edit]
Foetal demise occurs if the circulating blood volume is decreased significantly. The critical factor deciding the prognosis is the site of the hematoma and not the volume.[7] If discovered antenatally, serial USG and/or Doppler scans is indicated to monitor the size of the hematoma and well-being of the foetus.
## References[edit]
1. ^ Madu AE (2009). "Breus' mole in pregnancy". Journal of Obstetrics and Gynaecology. 26 (8): 815–816. doi:10.1080/01443610600987035. ISSN 0144-3615.
2. ^ Von Der Ahe, CV (1965). "The Breus mole". American Journal of Obstetrics and Gynecology. 92 (5): 699–701. doi:10.1016/0002-9378(65)90442-4. ISSN 0002-9378.
3. ^ Shanklin DR, Scott JS (June 1975). "Massive subchorial thrombohaematoma (Breus' mole)". Br J Obstet Gynaecol. 82 (6): 476–87. PMID 166651.
4. ^ Benirschke K, Peter Kaufmann P (2013-06-29). Pathology of the Human Placenta. Springer Science & Business Media. p. 243. ISBN 978-1-4757-4196-4.
5. ^ Kim DT, Riddell DC, Welch JP, Scott H, Fraser RB, Wright JR (2002). "Association between Breus' mole and partial hydatidiform mole: chance or can hydropic villi precipitate placental massive subchorionic thrombosis?". Pediatr Pathol Mol Med. 21 (5): 451–9. doi:10.1080/02770930290097507. PMID 12396900.
6. ^ Suchet IB (2013). "Breu's Mole". The Ultrasound of Life.
7. ^ Kojima K, Suzuki Y, Makino A, Murakami I, Suzumori K (2001). "A case of massive subchorionic thrombohematoma diagnosed by ultrasonography and magnetic resonance imaging". Fetal Diagn. Ther. 16 (1): 57–60. doi:10.1159/000053882. PMID 11125254.
## External links[edit]
Classification
D
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Breus' mole | c1390676 | 2,301 | wikipedia | https://en.wikipedia.org/wiki/Breus%27_mole | 2021-01-18T19:07:13 | {"umls": ["C1390676"], "wikidata": ["Q28439873"]} |
Hermansky–Pudlak syndrome
Other namesAlbinism with hemorrhagic diathesis and pigmented reticuloendothelial cells, Delta storage pool disease
Hermansky–Pudlak syndrome is inherited via autosomal recessive manner
SpecialtyEndocrinology
Heřmanský–Pudlák syndrome (often written Hermansky–Pudlak syndrome or abbreviated HPS) is an extremely rare autosomal recessive[1] disorder which results in oculocutaneous albinism (decreased pigmentation), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). It is considered to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800.[2] Many of the clinical research studies on the disease have been conducted in Puerto Rico.
There are eight classic forms of the disorder, based on the genetic mutation from which the disorder stems.[3]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 5.1 Considerations for patients
* 6 Prognosis
* 7 Research
* 8 Society
* 9 Eponym
* 10 See also
* 11 References
* 12 External links
## Signs and symptoms[edit]
There are three main disorders caused by Hermansky–Pudlak syndrome, which result in these symptoms:
* Albinism and eye problems: Individuals will have varying amounts of skin pigment (melanin). Because of the albinism there are eye problems such as light sensitivity (photophobia), strabismus (crossed eyes), and nystagmus (involuntary eye movements). Hermansky–Pudlak syndrome also impairs vision.[citation needed]
* Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.[citation needed]
* Cellular storage disorders: The syndrome causes a wax-like substance (ceroid) to accumulate in the body tissues and cause damage, especially in the lungs and kidneys.[4]
It is also associated with granulomatous colitis,[citation needed], an inflammation of the colon, and with pulmonary fibrosis,[citation needed] a potentially fatal lung disease.
## Causes[edit]
HPS can be caused by mutations in several genes: HPS1, HPS3, HPS4, HPS5, HPS6 and HPS7.[citation needed]
HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in the AP3B1 gene.[citation needed]
HPS type 7 may result from a mutation in the gene coding for dysbindin protein.[5]
Hermansky–Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP[dubious – discuss], responsible for this disorder is located on the long arm of chromosome 10 (10q2). Some research suggests that an abnormality of lysosomal function may be responsible for the development of the disease.
HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1 and Biogenesis of Lysosome-related Organelles Complex (BLOC1, BLOC1S2 and BLOC3) are associated with Hermansky–Pudlak syndrome.[citation needed]
In autosomal recessive disorders, the condition does not appear unless a person inherits two copies of the defective gene responsible for the disorder, one copy coming from each parent. If an individual receives one normal gene and one gene for the disorder, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.[6]
## Pathophysiology[edit]
The mechanism of Hermansky–Pudlak syndrome indicates that platelets in affected individuals accumulate abnormally with thrombin, epinephrine, and adenosine diphosphate, furthermore platelets in these individuals have a lower amount of dense bodies[7]
## Diagnosis[edit]
The diagnosis of HPS is established by clinical findings of hypopigmentation of the skin and hair, characteristic eye findings, and demonstration of absent dense bodies on whole mount electron microscopy of platelets. Molecular genetic testing of the HPS1 gene is available on a clinical basis for individuals from northwestern Puerto Rico. Molecular testing of the HPS3 gene is available on a clinical basis for individuals of central Puerto Rican or Ashkenazi Jewish heritage. Sequence analysis is available on a clinical basis for mutations in HPS1 and HPS4. Diagnosis of individuals with other types of HPS is available on a research basis only.[8]
## Treatment[edit]
While there is no cure for HPS, treatment for chronic hemorrhages associated with the disorder includes therapy with vitamin E and the antidiuretic dDAVP.[9]
### Considerations for patients[edit]
A preoperative pulmonology consultation is needed. The anesthesia team should be aware that patients may have postoperative pulmonary complications as part of the syndrome.[citation needed]
Preoperative hematology consultation is advisable prior to elective ocular surgeries. Since patients with the syndrome have bleeding tendencies, intraoperative, perioperative, and postoperative hemorrhages should be prevented and treated. If platelet aggregation improves with desmopressin, it may be administered in the preoperative period. However, sometimes plasmapheresis is needed in the perioperative period.[citation needed]
Ophthalmologists should try to avoid retrobulbar blocks in patients with the syndrome. Whenever possible, patients with HPS may benefit from general endotracheal anesthesia. Phacoemulsification may help prevent intraoperative and postoperative bleeding in patients with the syndrome. Prolonged bleeding has been reported following strabismus surgery in patients with the syndrome. [10]
## Prognosis[edit]
The course of HPS has been mild in rare instances of the disorder,[11] however, the general prognosis is still considered to be poor.[citation needed]
The disease can cause dysfunctions of the lungs, intestine, kidneys, and heart. The major complication of most forms of the disorder is pulmonary fibrosis, which typically exhibits in patients ages 40–50 years.[12] This is a fatal complication seen in many forms of HPS, and is the usual cause of death from the disorder.[13] HPS patients who develop pulmonary fibrosis typically have type 1 or type 4.[citation needed]
## Research[edit]
HPS is one of the rare lung diseases currently being studied by The Rare Lung Diseases Consortium (RLDC). The RLDC is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), of the National Center for Advancing Translational Sciences (NCATS). The RLDC is dedicated to developing new diagnostics and therapeutics for patients with rare lung diseases, through collaboration between the NIH, patient organizations and clinical investigators.[citation needed]
## Society[edit]
Hermansky–Pudlak syndrome patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases.[citation needed]
## Eponym[edit]
It is named for František Heřmanský (1916–1980) and Pavel Pudlák (1927–1993).[14][15][16]
## See also[edit]
* Biogenesis of lysosome-related organelles complex 1
* List of cutaneous conditions
## References[edit]
1. ^ Oh, J; Ho, L; Ala-Mello, S; Amato, D; Armstrong, L; Bellucci, S; Carakushansky, G; Ellis, Jp; Fong, Ct; Green, Js; Heon, E; Legius, E; Levin, Av; Nieuwenhuis, Hk; Pinckers, A; Tamura, N; Whiteford, Ml; Yamasaki, H; Spritz, Ra (March 1998). "Mutation analysis of patients with Hermansky–Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity". American Journal of Human Genetics. 62 (3): 593–8. doi:10.1086/301757. PMC 1376951. PMID 9497254.
2. ^ Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, et al. (January 2006). "Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky–Pudlak syndrome type 1 and 3 mutations in Puerto Rico". J. Invest. Dermatol. 126 (1): 85–90. doi:10.1038/sj.jid.5700034. PMC 3560388. PMID 16417222.
3. ^ Online Mendelian Inheritance in Man (OMIM): 203300
4. ^ "Hermansky–Pudlak Syndrome". Retrieved 24 November 2008.
5. ^ Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O'Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, Jenkins NA, Amato D, Roe BA, Starcevic M, Dell'Angelica EC, Elliott RW, Mishra V, Kingsmore SF, Paylor RE, Swank RT (2003). "Hermansky–Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1)". Nat. Genet. 35 (1): 84–9. doi:10.1038/ng1229. PMC 2860733. PMID 12923531.
6. ^ "CIGNA - Hermansky–Pudlak Syndrome". Retrieved 24 November 2008.
7. ^ "Hermansky-Pudlak Syndrome: Background, Pathophysiology, Epidemiology". 13 June 2017. Cite journal requires `|journal=` (help)
8. ^ Hermansky–Pudlak Syndrome. University of Washington, Seattle. 1993. Retrieved 24 November 2008.
9. ^ Wijermans, Pw; Van Dorp, Db (March 1989). "Hermansky–Pudlak syndrome: correction of bleeding time by 1-desamino-8D-arginine vasopressin". American Journal of Hematology. 30 (3): 154–7. doi:10.1002/ajh.2830300307. ISSN 0361-8609. PMID 2916560.
10. ^ "Hermansky–Pudlak Syndrome". Retrieved 24 November 2008.
11. ^ Schallreuter, Ku; Frenk, E; Wolfe, Ls; Witkop, Cj; Wood, Jm (1993). "Hermansky–Pudlak syndrome in a Swiss population" (Free full text). Dermatology. 187 (4): 248–56. doi:10.1159/000247258. ISSN 1018-8665. PMID 8274781.[permanent dead link]
12. ^ Depinho, Ra; Kaplan, Kl (May 1985). "The Hermansky–Pudlak syndrome. Report of three cases and review of pathophysiology and management considerations". Medicine. 64 (3): 192–202. doi:10.1097/00005792-198505000-00004. ISSN 0025-7974. PMID 3921802. S2CID 20833320.
13. ^ Davies, Bh; Tuddenham, Eg (April 1976). "Familial pulmonary fibrosis associated with oculocutaneous albinism and platelet function defect. A new syndrome". The Quarterly Journal of Medicine. 45 (178): 219–32. ISSN 0033-5622. PMID 940919.
14. ^ synd/2220 at Who Named It?
15. ^ Hermansky, F; Pudlak, P (1 February 1959). "Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies" (Free full text). Blood. 14 (2): 162–9. doi:10.1182/blood.V14.2.162.162. ISSN 0006-4971. PMID 13618373.[permanent dead link]
16. ^ Khalid Al Aboud; Daifullah Al Aboud (19 June 2013). "EPONYMS IN THE DERMATOLOGY LITERATURE LINKED TO CZECH REPUBLIC" (Free full text). Our Dermatology. 4 (2): 426–8.
## External links[edit]
* GeneReviews/NCBI/NIH/UW entry on Hermansky-Pudlak Syndrome
Classification
D
* ICD-10: E70.3
(ILDS E70.360)
* ICD-10-CM: E70.331
* ICD-9-CM: 270.2
* OMIM: 203300
* MeSH: D022861
* DiseasesDB: 29161
* SNOMED CT: 9311003
External resources
* eMedicine: oph/713 derm/925
* GeneReviews: Hermansky-Pudlak Syndrome
* Orphanet: 79430
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
* v
* t
* e
Disorders of bleeding and clotting
Coagulation · coagulopathy · Bleeding diathesis
Clotting
By cause
* Clotting factors
* Antithrombin III deficiency
* Protein C deficiency
* Activated protein C resistance
* Protein S deficiency
* Factor V Leiden
* Prothrombin G20210A
* Platelets
* Sticky platelet syndrome
* Thrombocytosis
* Essential thrombocythemia
* DIC
* Purpura fulminans
* Antiphospholipid syndrome
Clots
* Thrombophilia
* Thrombus
* Thrombosis
* Virchow's triad
* Trousseau sign of malignancy
By site
* Deep vein thrombosis
* Bancroft's sign
* Homans sign
* Lisker's sign
* Louvel's sign
* Lowenberg's sign
* Peabody's sign
* Pratt's sign
* Rose's sign
* Pulmonary embolism
* Renal vein thrombosis
Bleeding
By cause
Thrombocytopenia
* Thrombocytopenic purpura: ITP
* Evans syndrome
* TM
* TTP
* Upshaw–Schulman syndrome
* Heparin-induced thrombocytopenia
* May–Hegglin anomaly
Platelet function
* adhesion
* Bernard–Soulier syndrome
* aggregation
* Glanzmann's thrombasthenia
* platelet storage pool deficiency
* Hermansky–Pudlak syndrome
* Gray platelet syndrome
Clotting factor
* Hemophilia
* A/VIII
* B/IX
* C/XI
* von Willebrand disease
* Hypoprothrombinemia/II
* Factor VII deficiency
* Factor X deficiency
* Factor XII deficiency
* Factor XIII deficiency
* Dysfibrinogenemia
* Congenital afibrinogenemia
Signs and symptoms
* Bleeding
* Bruise
* Hematoma
* Petechia
* Purpura
* Nonthrombocytopenic purpura
By site
* head
* Epistaxis
* Hemoptysis
* Intracranial hemorrhage
* Hyphema
* Subconjunctival hemorrhage
* torso
* Hemothorax
* Hemopericardium
* Pulmonary hematoma
* abdomen
* Gastrointestinal bleeding
* Hemobilia
* Hemoperitoneum
* Hematocele
* Hematosalpinx
* joint
* Hemarthrosis
* v
* t
* e
Pigmentation disorders/Dyschromia
Hypo-/
leucism
Loss of
melanocytes
Vitiligo
* Quadrichrome vitiligo
* Vitiligo ponctué
Syndromic
* Alezzandrini syndrome
* Vogt–Koyanagi–Harada syndrome
Melanocyte
development
* Piebaldism
* Waardenburg syndrome
* Tietz syndrome
Loss of melanin/
amelanism
Albinism
* Oculocutaneous albinism
* Ocular albinism
Melanosome
transfer
* Hermansky–Pudlak syndrome
* Chédiak–Higashi syndrome
* Griscelli syndrome
* Elejalde syndrome
* Griscelli syndrome type 2
* Griscelli syndrome type 3
Other
* Cross syndrome
* ABCD syndrome
* Albinism–deafness syndrome
* Idiopathic guttate hypomelanosis
* Phylloid hypomelanosis
* Progressive macular hypomelanosis
Leukoderma w/o
hypomelanosis
* Vasospastic macule
* Woronoff's ring
* Nevus anemicus
Ungrouped
* Nevus depigmentosus
* Postinflammatory hypopigmentation
* Pityriasis alba
* Vagabond's leukomelanoderma
* Yemenite deaf-blind hypopigmentation syndrome
* Wende–Bauckus syndrome
Hyper-
Melanin/
Melanosis/
Melanism
Reticulated
* Dermatopathia pigmentosa reticularis
* Pigmentatio reticularis faciei et colli
* Reticulate acropigmentation of Kitamura
* Reticular pigmented anomaly of the flexures
* Naegeli–Franceschetti–Jadassohn syndrome
* Dyskeratosis congenita
* X-linked reticulate pigmentary disorder
* Galli–Galli disease
* Revesz syndrome
Diffuse/
circumscribed
* Lentigo/Lentiginosis: Lentigo simplex
* Liver spot
* Centrofacial lentiginosis
* Generalized lentiginosis
* Inherited patterned lentiginosis in black persons
* Ink spot lentigo
* Lentigo maligna
* Mucosal lentigines
* Partial unilateral lentiginosis
* PUVA lentigines
* Melasma
* Erythema dyschromicum perstans
* Lichen planus pigmentosus
* Café au lait spot
* Poikiloderma (Poikiloderma of Civatte
* Poikiloderma vasculare atrophicans)
* Riehl melanosis
Linear
* Incontinentia pigmenti
* Scratch dermatitis
* Shiitake mushroom dermatitis
Other/
ungrouped
* Acanthosis nigricans
* Freckle
* Familial progressive hyperpigmentation
* Pallister–Killian syndrome
* Periorbital hyperpigmentation
* Photoleukomelanodermatitis of Kobori
* Postinflammatory hyperpigmentation
* Transient neonatal pustular melanosis
Other
pigments
Iron
* Hemochromatosis
* Iron metallic discoloration
* Pigmented purpuric dermatosis
* Schamberg disease
* Majocchi's disease
* Gougerot–Blum syndrome
* Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis
* Lichen aureus
* Angioma serpiginosum
* Hemosiderin hyperpigmentation
Other
metals
* Argyria
* Chrysiasis
* Arsenic poisoning
* Lead poisoning
* Titanium metallic discoloration
Other
* Carotenosis
* Tar melanosis
Dyschromia
* Dyschromatosis symmetrica hereditaria
* Dyschromatosis universalis hereditaria
See also
* Skin color
* Skin whitening
* Tanning
* Sunless
* Tattoo
* removal
* Depigmentation
* v
* t
* e
Inherited disorders of trafficking / vesicular transport proteins
Vesicle formation
Lysosome/Melanosome:
* HPS1–HPS7
* Hermansky–Pudlak syndrome
* LYST
* Chédiak–Higashi syndrome
COPII:
* SEC23A
* Cranio-lenticulo-sutural dysplasia
* COG7
* CDOG IIE
APC:
* AP1S2
* X-linked intellectual disability
* AP3B1
* Hermansky–Pudlak syndrome 2
* AP4M1
* CPSQ3
Rab
* ARL6
* BBS3
* RAB27A
* Griscelli syndrome 2
* CHM
* Choroideremia
* MLPH
* Griscelli syndrome 3
Cytoskeleton
Myosin:
* MYO5A
* Griscelli syndrome 1
Microtubule:
* SPG4
* Hereditary spastic paraplegia 4
Kinesin:
* KIF5A
* Hereditary spastic paraplegia 10
Spectrin:
* SPTBN2
* Spinocerebellar ataxia 5
Vesicle fusion
Synaptic vesicle:
* SNAP29
* CEDNIK syndrome
* STX11
* Hemophagocytic lymphohistiocytosis 4
Caveolae:
* CAV1
* Congenital generalized lipodystrophy 3
* CAV3
* Limb-girdle muscular dystrophy 2B, Long QT syndrome 9
Vacuolar protein sorting:
* VPS33B
* ARC syndrome
* VPS13B
* Cohen syndrome
* DYSF
* Distal muscular dystrophy
See also vesicular transport proteins
*[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
| Hermansky–Pudlak syndrome | c0079504 | 2,302 | wikipedia | https://en.wikipedia.org/wiki/Hermansky%E2%80%93Pudlak_syndrome | 2021-01-18T18:32:22 | {"gard": ["6643"], "mesh": ["D022861"], "umls": ["C0079504"], "orphanet": ["231537", "79430", "231531", "280663"], "wikidata": ["Q1506216"]} |
Benign familial neonatal-infantile seizures (BFNIS) is a benign familial epilepsy syndrome with an intermediate phenotype between benign familial neonatal seizures (BFNS) and benign familial infantile seizures (BFIS; see these terms). So far, this syndrome has been described in multiple members of 10 families. Age of onset in these BFNIS families varied from 2 days to 6 months, with spontaneous resolution in most cases before the age of 12 months. Like BFNS and BFIS, seizures in BFNIS generally occur in clusters over one or a few days with posterior focal seizure onset. BFNIS is caused by mutations in the SCN2A gene (2q24.3), encoding the voltage-gated sodium channel alpha-subunit Na(V)1.2. Transmission is autosomal dominant.
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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
| Benign familial neonatal-infantile seizures | c0220669 | 2,303 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=140927 | 2021-01-23T19:01:58 | {"gard": ["1518"], "mesh": ["D020936"], "omim": ["607745"], "umls": ["C0220669"], "icd-10": ["G40.4"], "synonyms": ["BFNIS", "Benign neonatal-infantile epilepsy"]} |
Myelodysplastic syndrome with excess blasts is a rare type of myelodysplastic syndrome (MDS). In this type of MDS, the number of very early forms of blood cells (blasts) are increased in the bone marrow and/or blood. There is also a low numbers of at least one type of blood cell. The early forms of cell types in the bone marrow (red blood cells, white blood cells, or platelets) may or may not look abnormal (dysplasia) under the microscope. Signs and symptoms may include a very hard to treat and persistent anemia (refractory anemia), frequent infections (due to low numbers of neutrophils), easy bruising and bleeding (due to low number or abnormal platelets). MDS with excess blasts is one of the MDS most likely to turn into acute myeloid leukemia (AML). It is classified into 2 types, based on how many of the cells in the bone marrow or blood are blasts:
* MDS-EB1: blasts make up 5% to 9% of the cells in the bone marrow, or 2% to 4% of the cells in the blood
* MDS-EB2: blasts make up 10% to 19% of the cells in the bone marrow, or 5% to 19% of the cells in the blood; this type has a higher risk to become AML.
Some cases of MDS are linked to known risk factors (such as smoking, chemotherapy, having a genetic syndrome that increases the chance of developing MDS and other). These factors lead to changes in the DNA in bone marrow cells may cause MDS to develop, but most often, the cause is unknown. Treatment may include blood transfusions, supportive care, chemotherapy, radiotherapy and bone marrow transplant.[ 14773]
*[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
| Myelodysplastic Syndrome With Excess Blasts | c0002894 | 2,304 | gard | https://rarediseases.info.nih.gov/diseases/13578/myelodysplastic-syndrome-with-excess-blasts | 2021-01-18T17:58:51 | {"mesh": ["D000754"], "icd-10": ["D46-2"], "orphanet": ["86839"], "synonyms": ["Refractory anemia with excess blasts", "RAEB"]} |
This article is written like a personal reflection, personal essay, or argumentative essay that states a Wikipedia editor's personal feelings or presents an original argument about a topic. Please help improve it by rewriting it in an encyclopedic style. (July 2008) (Learn how and when to remove this template message)
Epilepsia partialis continua
Other namesKojevnikov's or Kozhevnikov's epilepsia
SpecialtyNeurology
Epilepsia partialis continua is a rare[1] type of brain disorder in which a patient experiences recurrent motor epileptic seizures that are focal (hands and face), and recur every few seconds or minutes for extended periods (days to years).
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
During these seizures, there is repetitive focal myoclonus or Jacksonian march. After a seizure has subsided, Todd's phenomenon may be observed, which includes transient unilateral weakness.
## Causes[edit]
There are numerous causes for this kind of seizure and they differ depending somewhat on the age at which the seizures begin. Epilepsy most often occurs at the extremes of life – in childhood or in very old age – but can develop at any time throughout one's life.
Although these seizures are usually due to large, acute brain lesions resulting from strokes in adults and focal cortical inflammatory processes in children (Rasmussen's encephalitis), possibly caused by chronic viral infections, edema, or autoimmune processes.
They are very medication and therapy-resistant, and the primary therapeutic goal is to stop secondary generalization. There are also many other reasons why these seizures occur. For example, they could be due to genetics, infections, or problems with brain development. Commonly the cause is unknown.
Genetic background determines such features as height, eye color, and potential to develop certain diseases like diabetes, but it also determines all the chemicals and structures that make up the brain, therefore playing a role in epilepsia partialis continua. The chemicals and structures that make up the brain have similarities across different people, but they vary in certain enzymes and receptors. These variations are not usually enough to cause a problem, but occasionally they do. For example, if a person has a mutation in a gene that creates the sodium channel (a part of the neuron required for firing) it makes it easier for neuronal firing to get out of control.
An infection of the brain (encephalitis) can also be a contributing factor. Although this sort of infection is uncommon it can be due to a virus, bacterium, or (very rarely) fungus. If a seizure happens during the infection itself, the person most likely doesn't have epilepsy but has "symptomatic seizures" or seizures occurring because of a known injury to the brain. Once the infection is stopped the seizures will stop. Another more common infection is "meningitis", infection of the membranes surrounding the brain. Since this infection does not directly involve the brain it might not appear as a possible cause of epilepsy, but has been shown that meningitis can cause epilepsy, which would give rise to the possibility of developing epilepsy partialis continua. These infections are most likely to result in epilepsy when they occur at an early age.
Problems with brain development can also be a factor. The brain undergoes a complicated process during development in which neurons are born and must travel to the surface of the brain. Here they wind up carefully placed in six distinct layers of the cerebral cortex. Throughout the brain, the placement of these neurons is normally quite precise. If this system doesn't work exactly right, neurons can develop outside their appropriate areas. If this happens then the firing or circuitry of the brain is not right, and an abnormal, epileptic circuit can result.
## Treatment[edit]
Identification of the underlying cause plays an important role in treatment. Brain abscesses or tumors can be—at least temporarily or partially, if not fully and permanently—surgically treated and chemotherapy and/or radiotherapy is given to the patient. If seizures do continue, various anticonvulsant medication regimens that can be tolerated by the patient can be tested and if need be, administered, either orally, or in emergency conditions such as status epilepticus after tonic-clonic (grand mal) seizures, intravenously. If stroke or other similar, transient disorders occur (cerebrovascular accident, or transient ischemic attack, TIA), then neurological imaging of the affected lobes or hemispheres of the brain can be performed (CT, MRI, PET, etc.) and, if not absolutely contraindicated, antithrombolytic therapy might be given if it can be tolerated due to the seizures; if a hemorrhagic stroke has occurred and surgery can be performed to cauterize the vessel or otherwise stop the bleeding, it will be attempted if it can be done safely.[2]
## References[edit]
1. ^ Bien CG, Elger CE (March 2008). "Epilepsia partialis continua: semiology and differential diagnoses". Epileptic Disord. 10 (1): 3–7. doi:10.1684/epd.2008.0161 (inactive 2021-01-10). PMID 18367424.CS1 maint: DOI inactive as of January 2021 (link)
2. ^ Sinha S, Satishchandra P (April 2007). "Epilepsia Partialis Continua over last 14 years: experience from a tertiary care center from south India". Epilepsy Res. 74 (1): 55–9. doi:10.1016/j.eplepsyres.2006.12.003. PMID 17292588. S2CID 25858396.
## External links[edit]
Classification
D
* ICD-10: G40.5
* ICD-9-CM: 345.7
* MeSH: D017036
External resources
* eMedicine: neuro/653
* v
* t
* e
Seizures and epilepsy
Basics
* Seizure types
* Aura (warning sign)
* Postictal state
* Epileptogenesis
* Neonatal seizure
* Epilepsy in children
Management
* Anticonvulsants
* Investigations
* Electroencephalography
* Epileptologist
Personal issues
* Epilepsy and driving
* Epilepsy and employment
Seizure types
Focal
Seizures
Simple partial
Complex partial
Gelastic seizure
Epilepsy
Temporal lobe epilepsy
Frontal lobe epilepsy
Rolandic epilepsy
Nocturnal epilepsy
Panayiotopoulos syndrome
Vertiginous epilepsy
Generalised
* Tonic–clonic
* Absence seizure
* Atonic seizure
* Automatism
* Benign familial neonatal seizures
* Lennox–Gastaut syndrome
* Myoclonic astatic epilepsy
* Epileptic spasms
Status epilepticus
* Epilepsia partialis continua
* Complex partial status epilepticus
Myoclonic epilepsy
* Progressive myoclonus epilepsy
* Dentatorubral–pallidoluysian atrophy
* Unverricht–Lundborg disease
* MERRF syndrome
* Lafora disease
* Juvenile myoclonic epilepsy
Non-epileptic seizure
* Febrile seizure
* Psychogenic non-epileptic seizure
Related disorders
* Sudden unexpected death in epilepsy
* Todd's paresis
* Landau–Kleffner syndrome
* Epilepsy in animals
Organizations
* Citizens United for Research in Epilepsy (US)
* Epilepsy Action (UK)
* Epilepsy Action Australia
* Epilepsy Foundation (US)
* Epilepsy Outlook (UK)
* Epilepsy Research UK
* Epilepsy Society (UK)
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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
| Epilepsia partialis continua | c0085543 | 2,305 | wikipedia | https://en.wikipedia.org/wiki/Epilepsia_partialis_continua | 2021-01-18T18:29:14 | {"mesh": ["D017036"], "umls": ["C0085543"], "icd-9": ["345.71", "345.7"], "icd-10": ["G40.5"], "wikidata": ["Q4898733"]} |
Xanthoma striatum palmare
SpecialtyDermatology
Xanthoma striatum palmare is a cutaneous condition characterized by xanthomas of the palmar creases which are almost diagnostic for dysbetalipoproteinemia.[1]
Xanthomas consist of accumulations of lipids within macrophages deposited within the dermis of the skin.
## See also[edit]
* Xanthoma tendinosum
* List of cutaneous conditions
* List of xanthoma variants associated with hyperlipoproteinemia subtypes
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1416. ISBN 978-1-4160-2999-1.
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
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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
| Xanthoma striatum palmare | c4476834 | 2,306 | wikipedia | https://en.wikipedia.org/wiki/Xanthoma_striatum_palmare | 2021-01-18T18:43:31 | {"wikidata": ["Q8043040"]} |
This article's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (September 2013) (Learn how and when to remove this template message)
Aboulomania (from Greek a– 'without', and boulē 'will')[1] is a mental disorder in which the patient displays pathological indecisiveness.[2][3] It is typically associated with anxiety, stress, depression, and mental anguish, and can severely affect one's ability to function socially. Although many people suffer from indecision, it is rarely to the extent of obsession.[4] The part of the brain that is tied to making rational choices, the prefrontal cortex, can hold several pieces of information at any given time.[4] This may quickly overwhelm somebody when trying to make decisions, regardless of the importance of that decision. They come up with reasons that their decisions will turn out badly, causing them to over-analyze every situation critically in a classic case of paralysis by analysis. Lack of information, valuation difficulty, and outcome uncertainty can become an obsession.[5]
Researchers speculate extremely authoritarian or overprotective parenting can lead to the development of Aboulomania. They believe the disorder is a result of overinvolvement and intrusive behaviours. The caretakers who have caused this extreme dependency may have rewarded loyalty and punished the child or patient for independence. It is thought the family of the diagnosed might also avoid expressing emotions and neglect to demonstrate properly defined relational roles in the family. [6]
This psychology-related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
## References[edit]
1. ^ "aboulia". The New Oxford American Dictionary (2nd ed.).
2. ^ Chrisomalis, Stephen (2007). "Manias and Obsessions". The Phronistery.
3. ^ Rawat, P.S. (2002). Midline Medical History. Jane Publishers. p. 11. ISBN 9788131903537.
4. ^ a b 2010, Jennifer Byrne. "How to Overcome Indecision". Livestrong.CS1 maint: numeric names: authors list (link)
5. ^ Rassin, Eric. "A psychological theory of indecisiveness". Netherlands Journal of Psychology. 63 (1): 1–11. doi:10.1007/BF03061056.
Look up aboulomania in Wiktionary, the free dictionary.
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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
| Aboulomania | None | 2,307 | wikipedia | https://en.wikipedia.org/wiki/Aboulomania | 2021-01-18T18:31:37 | {"wikidata": ["Q4668562"]} |
medical condition
Acneiform eruption
SpecialtyDermatology
Acneiform eruptions are a group of dermatoses including acne vulgaris, rosacea, folliculitis, and perioral dermatitis.[1] Restated, acneiform eruptions are follicular eruptions characterized by papules and pustules resembling acne.[2] The hybrid term acneiform, literally, refers to an appearance similar to acne.[3]
The terminology used in this field can be complex, and occasionally contradictory. Some sources consider acne vulgaris part of the differential diagnosis for an acneiform eruption.[4] Other sources classified acne vulgaris under acneiform eruption.[5] MeSH explicitly excludes perioral dermatitis from the category of "acneiform eruptions",[6] though it does group acneiform eruptions and perioral dermatitis together under "facial dermatoses".
## See also[edit]
* Drug eruption
* List of cutaneous conditions
## References[edit]
1. ^ Cheung MJ, Taher M, Lauzon GJ (April 2005). "Acneiform facial eruptions: a problem for young women". Can Fam Physician. 51: 527–33. PMC 1472951. PMID 15856972.
2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 241. ISBN 0-7216-2921-0.
3. ^ "acneiform" at Dorland's Medical Dictionary
4. ^ "eMedicine - Acneiform Eruptions : Article by Julianne H Kuflik". February 2019. Cite journal requires `|journal=` (help)
5. ^ Acneiform+eruption at the US National Library of Medicine Medical Subject Headings (MeSH)
6. ^ Facial+Dermatoses at the US National Library of Medicine Medical Subject Headings (MeSH)
## External links[edit]
Classification
D
* MeSH: D017486
External resources
* eMedicine: derm/620
* v
* t
* e
Disorders of skin appendages
Nail
* thickness: Onychogryphosis
* Onychauxis
* color: Beau's lines
* Yellow nail syndrome
* Leukonychia
* Azure lunula
* shape: Koilonychia
* Nail clubbing
* behavior: Onychotillomania
* Onychophagia
* other: Ingrown nail
* Anonychia
* ungrouped: Paronychia
* Acute
* Chronic
* Chevron nail
* Congenital onychodysplasia of the index fingers
* Green nails
* Half and half nails
* Hangnail
* Hapalonychia
* Hook nail
* Ingrown nail
* Lichen planus of the nails
* Longitudinal erythronychia
* Malalignment of the nail plate
* Median nail dystrophy
* Mees' lines
* Melanonychia
* Muehrcke's lines
* Nail–patella syndrome
* Onychoatrophy
* Onycholysis
* Onychomadesis
* Onychomatricoma
* Onychomycosis
* Onychophosis
* Onychoptosis defluvium
* Onychorrhexis
* Onychoschizia
* Platonychia
* Pincer nails
* Plummer's nail
* Psoriatic nails
* Pterygium inversum unguis
* Pterygium unguis
* Purpura of the nail bed
* Racquet nail
* Red lunulae
* Shell nail syndrome
* Splinter hemorrhage
* Spotted lunulae
* Staining of the nail plate
* Stippled nails
* Subungual hematoma
* Terry's nails
* Twenty-nail dystrophy
Hair
Hair loss/
Baldness
* noncicatricial alopecia: Alopecia
* areata
* totalis
* universalis
* Ophiasis
* Androgenic alopecia (male-pattern baldness)
* Hypotrichosis
* Telogen effluvium
* Traction alopecia
* Lichen planopilaris
* Trichorrhexis nodosa
* Alopecia neoplastica
* Anagen effluvium
* Alopecia mucinosa
* cicatricial alopecia: Pseudopelade of Brocq
* Central centrifugal cicatricial alopecia
* Pressure alopecia
* Traumatic alopecia
* Tumor alopecia
* Hot comb alopecia
* Perifolliculitis capitis abscedens et suffodiens
* Graham-Little syndrome
* Folliculitis decalvans
* ungrouped: Triangular alopecia
* Frontal fibrosing alopecia
* Marie Unna hereditary hypotrichosis
Hypertrichosis
* Hirsutism
* Acquired
* localised
* generalised
* patterned
* Congenital
* generalised
* localised
* X-linked
* Prepubertal
Acneiform
eruption
Acne
* Acne vulgaris
* Acne conglobata
* Acne miliaris necrotica
* Tropical acne
* Infantile acne/Neonatal acne
* Excoriated acne
* Acne fulminans
* Acne medicamentosa (e.g., steroid acne)
* Halogen acne
* Iododerma
* Bromoderma
* Chloracne
* Oil acne
* Tar acne
* Acne cosmetica
* Occupational acne
* Acne aestivalis
* Acne keloidalis nuchae
* Acne mechanica
* Acne with facial edema
* Pomade acne
* Acne necrotica
* Blackhead
* Lupus miliaris disseminatus faciei
Rosacea
* Perioral dermatitis
* Granulomatous perioral dermatitis
* Phymatous rosacea
* Rhinophyma
* Blepharophyma
* Gnathophyma
* Metophyma
* Otophyma
* Papulopustular rosacea
* Lupoid rosacea
* Erythrotelangiectatic rosacea
* Glandular rosacea
* Gram-negative rosacea
* Steroid rosacea
* Ocular rosacea
* Persistent edema of rosacea
* Rosacea conglobata
* variants
* Periorificial dermatitis
* Pyoderma faciale
Ungrouped
* Granulomatous facial dermatitis
* Idiopathic facial aseptic granuloma
* Periorbital dermatitis
* SAPHO syndrome
Follicular cysts
* "Sebaceous cyst"
* Epidermoid cyst
* Trichilemmal cyst
* Steatocystoma
* simplex
* multiplex
* Milia
Inflammation
* Folliculitis
* Folliculitis nares perforans
* Tufted folliculitis
* Pseudofolliculitis barbae
* Hidradenitis
* Hidradenitis suppurativa
* Recurrent palmoplantar hidradenitis
* Neutrophilic eccrine hidradenitis
Ungrouped
* Acrokeratosis paraneoplastica of Bazex
* Acroosteolysis
* Bubble hair deformity
* Disseminate and recurrent infundibulofolliculitis
* Erosive pustular dermatitis of the scalp
* Erythromelanosis follicularis faciei et colli
* Hair casts
* Hair follicle nevus
* Intermittent hair–follicle dystrophy
* Keratosis pilaris atropicans
* Kinking hair
* Koenen's tumor
* Lichen planopilaris
* Lichen spinulosus
* Loose anagen syndrome
* Menkes kinky hair syndrome
* Monilethrix
* Parakeratosis pustulosa
* Pili (Pili annulati
* Pili bifurcati
* Pili multigemini
* Pili pseudoannulati
* Pili torti)
* Pityriasis amiantacea
* Plica neuropathica
* Poliosis
* Rubinstein–Taybi syndrome
* Setleis syndrome
* Traumatic anserine folliculosis
* Trichomegaly
* Trichomycosis axillaris
* Trichorrhexis (Trichorrhexis invaginata
* Trichorrhexis nodosa)
* Trichostasis spinulosa
* Uncombable hair syndrome
* Wooly hair nevus
Sweat
glands
Eccrine
* Miliaria
* Colloid milium
* Miliaria crystalline
* Miliaria profunda
* Miliaria pustulosa
* Miliaria rubra
* Occlusion miliaria
* Postmiliarial hypohidrosis
* Granulosis rubra nasi
* Ross’ syndrome
* Anhidrosis
* Hyperhidrosis
* Generalized
* Gustatory
* Palmoplantar
Apocrine
* Body odor
* Chromhidrosis
* Fox–Fordyce disease
Sebaceous
* Sebaceous hyperplasia
This cutaneous condition article 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
| Acneiform eruption | c0175167 | 2,308 | wikipedia | https://en.wikipedia.org/wiki/Acneiform_eruption | 2021-01-18T18:28:02 | {"mesh": ["D017486"], "umls": ["C0175167"], "icd-10": ["L70.8"], "wikidata": ["Q2365426"]} |
Splenogonadal fusion-limb defects-micrognatia syndrome is a rare dysostosis syndrome characterized by abnormal fusion of the spleen with the gonad (or more rarely with remnants of the mesonephros), limb abnormalities (consisting of amelia or severe reduction defects leading to upper and/or lower rudimentary limbs) and orofacial abnormalities such as cleft palate, bifid uvula, microglossia and mandibular hypoplasia. It could also be associated with other malformations such as cryptorchidism, anal stenosis/atresia, hypoplastic lungs and cardiac malformations.
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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
| Splenogonadal fusion-limb defects-micrognathia syndrome | c1866745 | 2,309 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2063 | 2021-01-23T17:08:19 | {"gard": ["4963"], "mesh": ["C537318"], "omim": ["183300"], "umls": ["C1866745"], "icd-10": ["Q87.8"], "synonyms": ["SGFLD syndrome"]} |
A number sign (#) is used with this entry because of evidence that trimethylaminuria, sometimes referred to as fish-odor syndrome, is caused by homozygous or compound heterozygous mutation in the gene encoding flavin-containing monooxygenase-3 (FMO3; 136132) on chromosome 1q24.
Another inborn error of metabolism accompanied by fish-like body odor results from deficiency of dimethylglycine dehydrogenase (see 605850).
Description
Trimethylaminuria results from the abnormal presence of large amounts of volatile and malodorous trimethylamine within the body. This chemical, a tertiary aliphatic amine, is excreted in the urine, sweat (ichthyohidrosis), and breath, which take on the offensive odor of decaying fish (Mitchell, 1996).
Clinical Features
Individuals with trimethylaminuria excrete relatively large amounts of amino-trimethylamine (TMA) in their urine, sweat, and breath, and exhibit a fishy body odor characteristic of the malodorous free amine, leading to the designation fish-odor syndrome. TMA is a product of intestinal bacterial action. The substrates from which it is derived are choline, which, bound to lecithin, is present most abundantly in egg yolk, liver, kidney, legumes, soy beans, and peas, as well as from trimethylamine-N-oxide, a normal constituent of saltwater fishes. Normally, TMA produced in the gut is absorbed and oxidized in the liver by FMO, a microsomal mixed-function oxidase (Higgins et al., 1972).
Humbert et al. (1970) first used the terms trimethylaminuria and fish-odor syndrome to describe a 6-year-old girl who intermittently had a fishy odor. She also had multiple pulmonary infections beginning in the neonatal period, the clinical stigmata of Turner syndrome but normal karyotype, splenomegaly, anemia, and neutropenia. Her urine contained increased amounts of TMA. In the same patient, Humbert et al. (1971) found defective membrane function in platelets, neutrophils, and red cells, and Higgins et al. (1972) found deficiency of trimethylamine oxidase by liver biopsy. Calvert (1973) noted that the features in the patient of Humbert et al. (1970) were those of Noonan syndrome (163950). He studied a clinically identical patient but found no trimethylaminuria with or without loading with trimethylamine. Witt et al. (1988) included the patient of Humbert et al. (1970) in their series of cases of Noonan syndrome with bleeding diathesis.
Lee et al. (1976) observed a brother and sister with trimethylaminuria; in both, an offensive fishy odor occurred when the mother was breast feeding them and had eaten eggs or fish. Danks et al. (1976) referred to 4 affected individuals in their personal experience.
Mayatepek and Kohlmuller (1998) described 2 unrelated children with transient trimethylaminuria. One was a 2-month-old female infant referred because of an offensive odor on her skin and from her urine which was noticed by the parents. When the child was 6 months old, the fishy odor completely disappeared. The second patient was a 4-year-old boy who was referred because of smelly urine and skin which had been noticed by his mother from about the age of 18 months. In these children, transient trimethylaminuria occurred without N-oxidation deficiency.
Zschocke et al. (1999) studied patients with mild trimethylaminuria and concluded that FMO3 deficiency is a spectrum of phenotypes that can include transient or mild malodor depending on environmental exposures. Mild FMO3 deficiency may have clinical relevance beyond intermittent body odor leading to an abnormal metabolism of drugs, hypertension, or increased cardiovascular disease risk.
Todd (1979) noted that patients with TMA may be deeply disturbed, depressed, and even suicidal, with psychosocial problems in school. Rehman (1999) also reported that patients with TMA often have psychosocial problems, including strong feelings of shame, embarrassment, low self-esteem, social isolation, anxiety, and depression.
Clinical Management
Treatment for trimethylaminuria can involve counseling, dietary adjustments, short-course treatment with metronidazole, neomycin, or lactulose, and the use of soaps with a pH value of 5.5-6.5 (Rehman, 1999).
Inheritance
Ayesh et al. (1993) studied 187 subjects with suspected body malodor and concluded that the trimethylaminuria is inherited as an autosomal recessive trait.
Diagnosis
Al-Waiz et al. (1987, 1988) presented evidence for deficiency in the N-oxidation of trimethylamine in persons with trimethylaminuria. The parents of affected persons showed partial impairment of N-oxidation on substrate challenge. They found 2 possible carriers among 169 randomly screened persons. N-oxidation is an important route of biotransformation for many substances including nicotinamide, nicotine, guanethidine, and metyrapone. Al-Waiz et al. (1989) described a TMA loading test for detection of carriers. Zhang et al. (1995) confirmed the oral trimethylamine challenge test for the identification of heterozygotes. Among 100 apparently normal volunteers who were challenged with trimethylamine, 1 had an N-oxidation capacity that fell within the range found among obligate heterozygotes.
Ayesh et al. (1993) studied 187 subjects with suspected body malodor ascertained in response to a newspaper story concerning the fish-odor syndrome. Biochemical tests were performed in 156 of the patients and 5 families of 6 of the subjects with the fish-odor syndrome agreed to further tests. The fish-odor syndrome was diagnosed in 11 subjects; the percentage of total trimethylamine excreted in their urine samples that was oxidized to trimethylamine N-oxide was less than 55% under normal dietary conditions and less than 25% after oral challenge with trimethylamine. In normal subjects, more than 80% of trimethylamine was N-oxidized. All parents of 6 subjects with the syndrome who were tested showed impaired N-oxidation of excreted trimethylamine after oral challenge, indicating that they were heterozygous carriers of the allele for the syndrome.
Mayatepek and Kohlmuller (1998) found that transient trimethylaminuria in 2 children occurred without N-oxidation deficiency. This demonstrated that a diagnosis of fish-odor syndrome should include the analysis of urinary excretion not only of trimethylamine but also of trimethylamine-N-oxide.
Molecular Genetics
Akerman et al. (1997) and Dolphin et al. (1997) demonstrated that trimethylaminuria is caused by mutation in the FMO3 gene (136132). One individual of British extraction was shown to be homozygous for an E305X mutation (136132.0001) of the FMO3 gene; this person, in addition to trimethylaminuria, had tachycardia and severe hypertension after eating cheese (which contains tyramine) and after using nasal epinephrine following an epistaxis (Danks et al., 1976). The FMO3 enzyme metabolizes tyramine.
Zschocke et al. (1999) examined the patients of Mayatepek and Kohlmuller (1998) with transient trimethylaminuria and other patients with mild trimethylaminuria and found compound heterozygosity for a missense mutation on one allele and 2 amino acid polymorphisms (E158K, E308G) on the other allele (see, e.g., 136132.0015). Zschocke et al. (1999) found that the variant allele with the 2 polymorphisms occurred in 20% and 6% of German and Turkish controls, respectively. The authors performed standardized TMA challenge tests in the controls with this variant allele and found markedly reduced FMO3 enzyme activity in vivo.
History
Reports of fish-like odor in people have been found in literature as far back as 1400-1000 B.C. in the Indian epic of the Bharata Dynasty, 'Mahabharata,' by Vyasa (Mitchell, 1996).
INHERITANCE \- Autosomal recessive CARDIOVASCULAR Heart \- Tachycardia after eating cheese (in some patients) Vascular \- hypertension, severe, after eating cheese (in some patients) RESPIRATORY Lung \- Pulmonary infections (in some patients) NEUROLOGIC Behavioral Psychiatric Manifestations \- Depression \- Suicidal \- Psychosocial problems in school HEMATOLOGY \- Anemia (in some patients) \- Neutropenia In some patients) LABORATORY ABNORMALITIES \- Trimethylaminuria \- Deficiency of FMO-mediated N-oxidation of amino-trimethylamine (TMA) derived from foodstuffs \- Large amounts of TMA in urine, sweat, and breath MISCELLANEOUS \- Offensive fishy body odor MOLECULAR BASIS \- Caused by mutation in the flavin-containing monooxygenase 3 gene (FMO3, 136132.0001 ) ▲ 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
| TRIMETHYLAMINURIA | c0342739 | 2,310 | omim | https://www.omim.org/entry/602079 | 2019-09-22T16:14:07 | {"doid": ["0080361"], "mesh": ["C536561"], "omim": ["602079"], "icd-10": ["E72.52"], "orphanet": ["468726"], "synonyms": ["Alternative titles", "FISH-ODOR SYNDROME"], "genereviews": ["NBK1103"]} |
Potassium-aggravated myotonia
Other namesPAM[1]
This condition is inherited in an autosomal dominant manner
Potassium-aggravated myotonia is a rare genetic disorder that affects skeletal muscle. [2]Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness, often painful, that worsens after exercise and may be aggravated by eating potassium-rich foods such as bananas and potatoes. Stiffness occurs in skeletal muscles throughout the body. Potassium-aggravated myotonia ranges in severity from mild episodes of muscle stiffness to severe, disabling disease with frequent attacks. Potassium-aggravated myotonia may, in some cases, also cause paradoxical myotonia, in which myotonia becomes more severe at the time of movement instead of after movement has ceased. Unlike some other forms of myotonia, potassium-aggravated myotonia is not associated with episodes of muscle weakness.[citation needed]
Mutations in the SCN4A gene cause potassium-aggravated myotonia. The SCN4A gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles contract and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged ions, including sodium, into skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate ion flow, increasing the movement of sodium ions into skeletal muscle cells. The influx of extra sodium ions triggers prolonged muscle contractions, which are the hallmark of myotonia.[citation needed]
Potassium-aggravated myotonia 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 some cases, an affected person inherits a mutation in the SCN4A gene from one affected parent. Other cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Potassium aggravated myotonia". www.orpha.net. Retrieved 30 September 2019.
2. ^ Reference, Genetics Home. "Potassium-aggravated myotonia". Genetics Home Reference. Retrieved 30 September 2019.
## External links[edit]
Classification
D
* ICD-10: G71.1
* OMIM: 608390
* MeSH: C538353
External resources
* Orphanet: 612
* v
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* e
Diseases of ion channels
Calcium channel
Voltage-gated
* CACNA1A
* Familial hemiplegic migraine 1
* Episodic ataxia 2
* Spinocerebellar ataxia type-6
* CACNA1C
* Timothy syndrome
* Brugada syndrome 3
* Long QT syndrome 8
* CACNA1F
* Ocular albinism 2
* CSNB2A
* CACNA1S
* Hypokalemic periodic paralysis 1
* Thyrotoxic periodic paralysis 1
* CACNB2
* Brugada syndrome 4
Ligand gated
* RYR1
* Malignant hyperthermia
* Central core disease
* RYR2
* CPVT1
* ARVD2
Sodium channel
Voltage-gated
* SCN1A
* Familial hemiplegic migraine 3
* GEFS+ 2
* Febrile seizure 3A
* SCN1B
* Brugada syndrome 6
* GEFS+ 1
* SCN4A
* Hypokalemic periodic paralysis 2
* Hyperkalemic periodic paralysis
* Paramyotonia congenita
* Potassium-aggravated myotonia
* SCN4B
* Long QT syndrome 10
* SCN5A
* Brugada syndrome 1
* Long QT syndrome 3
* SCN9A
* Erythromelalgia
* Febrile seizure 3B
* Paroxysmal extreme pain disorder
* Congenital insensitivity to pain
Constitutively active
* SCNN1B/SCNN1G
* Liddle's syndrome
* SCNN1A/SCNN1B/SCNN1G
* Pseudohypoaldosteronism 1AR
Potassium channel
Voltage-gated
* KCNA1
* Episodic ataxia 1
* KCNA5
* Familial atrial fibrillation 7
* KCNC3
* Spinocerebellar ataxia type-13
* KCNE1
* Jervell and Lange-Nielsen syndrome
* Long QT syndrome 5
* KCNE2
* Long QT syndrome 6
* KCNE3
* Brugada syndrome 5
* KCNH2
* Short QT syndrome
* KCNQ1
* Jervell and Lange-Nielsen syndrome
* Romano–Ward syndrome
* Short QT syndrome
* Long QT syndrome 1
* Familial atrial fibrillation 3
* KCNQ2
* BFNS1
Inward-rectifier
* KCNJ1
* Bartter syndrome 2
* KCNJ2
* Andersen–Tawil syndrome
* Long QT syndrome 7
* Short QT syndrome
* KCNJ11
* TNDM3
* KCNJ18
* Thyrotoxic periodic paralysis 2
Chloride channel
* CFTR
* Cystic fibrosis
* Congenital absence of the vas deferens
* CLCN1
* Thomsen disease
* Myotonia congenita
* CLCN5
* Dent's disease
* CLCN7
* Osteopetrosis A2, B4
* BEST1
* Vitelliform macular dystrophy
* CLCNKB
* Bartter syndrome 3
TRP channel
* TRPC6
* FSGS2
* TRPML1
* Mucolipidosis type IV
Connexin
* GJA1
* Oculodentodigital dysplasia
* Hallermann–Streiff syndrome
* Hypoplastic left heart syndrome
* GJB1
* Charcot–Marie–Tooth disease X1
* GJB2
* Keratitis–ichthyosis–deafness syndrome
* Ichthyosis hystrix
* Bart–Pumphrey syndrome
* Vohwinkel syndrome)
* GJB3/GJB4
* Erythrokeratodermia variabilis
* Progressive symmetric erythrokeratodermia
* GJB6
* Clouston's hidrotic ectodermal dysplasia
Porin
* AQP2
* Nephrogenic diabetes insipidus 2
See also: ion channels
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Potassium-aggravated myotonia | c2931826 | 2,311 | wikipedia | https://en.wikipedia.org/wiki/Potassium-aggravated_myotonia | 2021-01-18T18:30:51 | {"gard": ["4459"], "mesh": ["C538353"], "umls": ["C2931826"], "orphanet": ["612"], "wikidata": ["Q7234683"]} |
MEDNIK syndrome, previously known as Erythrokeratodermia Variabilis type 3 (EKV3), is characterized by intellectual deficit, enteropathy, sensorineural hearing loss, peripheral neuropathy, lamellar and erythrodermic ichthyosis, and keratodermia (MEDNIK stands for Mental retardation, Enteropathy, Deafness, peripheral Neuropathy, Ichtyosis, Keratodermia).
## Epidemiology
The syndrome has been described in four families descending from limited number of ancestors in Quebec.
## Etiology
The disease is due to a mutation in the AP1S1 gene encoding the small subunit sigma1A of the AP-1 complex.
## Genetic counseling
Transmission is autosomal recessive.
*[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
| MEDNIK syndrome | c1836330 | 2,312 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171851 | 2021-01-23T17:48:31 | {"mesh": ["C563739"], "omim": ["609313"], "umls": ["C1836330"], "synonyms": ["Intellectual disability-enteropathy-deafness-peripheral neuropathy-ichthyosis-keratodermia syndrome", "Intellectual disability-enteropathy-hearing loss-peripheral neuropathy-ichthyosis-keratodermia syndrome"]} |
A number sign (#) is used with this entry because of evidence that Teebi hypertelorism syndrome (TBHS) is caused by heterozygous mutation in the SPECC1L gene (614140) on chromosome 22q11.
Clinical Features
Teebi (1987) described a 4-generation Arab family in which many individuals showed striking hypertelorism with some other features suggesting craniofrontonasal syndrome (CFNS; 304110) or Aarskog syndrome (305400). Findings differentiating this disorder from the former condition were a nasal tip that was normal or at the most only slightly broad and no evidence of craniosynostosis or abnormalities of the fingernails. Findings differentiating it from the latter condition were more severe hypertelorism and absence of short stature and joint laxity. It was further distinguished from both CFNS and Aarskog syndrome by the fact that males and females were equally affected and the sex ratio was almost 1:1. In addition to hypertelorism, the disorder described by Teebi (1987) was characterized by prominent forehead, mild antimongoloid slant, long palpebral fissures, heavy and broad eyebrows, widow's peak (194000), broad and depressed nasal bridge, short nose, slightly small, broad hands, mild interdigital webbing, and shawl scrotum. There were several instances of male-to-male transmission.
Morris et al. (1987) described a 4-generation family in which 6 persons had frontonasal dysplasia with variable extracranial abnormalities. All affected persons had hypertelorism, bifid or broad nose, and highly arched palate. Cleft lip and palate were present in 1, Sprengel anomaly in 2, pseudarthrosis of the clavicle in 2, pectus excavatum in 3, diaphragmatic hernia in 2, broad first toe in 4, longitudinal grooves of the nails in 5, shawl scrotum in 2 of 3 males, 1 of whom had first-degree hypospadias, and mild retardation in 1. Morris et al. (1987) concluded that the family had craniofrontonasal syndrome, but McGaughran et al. (2002) suggested that the family may instead have had Teebi syndrome, since the affected males demonstrated additional anomalies not usually observed in CFNS.
Stratton (1991) described a US family with affected persons in 4 generations with instances of male-to-male transmission.
Tsukahara et al. (1995) described Teebi hypertelorism syndrome in a 6-year-old girl who also had ventricular septal defect, lipoma of the occipital area, and hypoplastic left cerebellar hemisphere. The father was thought to have mild manifestations of the condition.
Tsai et al. (2002) reported a family in which the mother and her daughter and son had Teebi hypertelorism syndrome with some previously unrecognized manifestations. The clinical findings included a prominent forehead, arched eyebrows, pronounced hypertelorism, long philtrum, mild interdigital webbing, fifth-finger clinodactyly, umbilical anomalies, and hypotonia. The mother and daughter also had ptosis requiring surgical correction. The mother had an umbilical hernia requiring surgical correction as a child and a history of heart murmur. The daughter had bilateral iridochorioretinal colobomas with high hyperopia and a small umbilical hernia. The son had less striking facial features but was born with a small omphalocele, large atrial septal defect secundum, patent ductus arteriosus (see 607411), bilateral cryptorchidism, right hydronephrosis, and a cystic left kidney.
Koenig (2003) reported a girl with Teebi syndrome, aged 2 years and 5 months, who had a prominent forehead, hypertelorism, mild exophthalmos, long palpebral fissures, depressed nasal bridge, broad nasal tip, long philtrum, and thin upper lip with everted lower lip. She also had a small chin, low-set ears with preauricular fistulas, short neck, and mild pectus excavatum. Clinodactyly of the fifth fingers with mild radial deviation of the distal phalanges of the middle fingers and mild pes adductus were present. Natal teeth and umbilical hernia had been observed. Ultrasound examination detected an ectopic right kidney. Psychomotor development was normal. Her mother and her grandmother had similar features, supporting autosomal dominant inheritance.
Han et al. (2006) reported a 4.5-year-old girl with clinical features of Teebi hypertelorism syndrome who required a pacemaker for third-degree atrioventricular block, a finding not reported in 36 patients previously diagnosed with Teebi hypertelorism syndrome. The authors reviewed data from 18 well-documented cases and noted a characteristic facial appearance with hypertelorism, heavy, broad, and arched eyebrows, a thin upper lip with a long and deep philtrum, and a prominent forehead. Structural cardiac defects were present in 5 patients.
Bhoj et al. (2015) reported 2 unrelated families with clinical features of Teebi hypertelorism syndrome. An affected mother and son in the first family had previously been reported by Hoffman et al. (2007) as having a distinct syndrome resembling Teebi hypertelorism and Aarskog syndromes. Features in the boy included hypertelorism, natal teeth, 2-vessel cord, left preauricular pit, micrognathia, hypersegmented lumbar vertebra, short stature, and a shawl scrotum. He had surgery to repair sagittal and coronal synostosis, bilateral ptosis, and a ventricular septal defect. He was also found to have a dilated aortic root at age 9 years. Although concern was initially raised for developmental delay, his last IQ testing performed at age 10 was in the normal range. His mother had hypertelorism, ptosis, bicornuate uterus, preauricular pit, and short stature. In the second family, the patient was diagnosed with Teebi hypertelorism syndrome at birth after hypertelorism, natal teeth, an atrial septal defect, a ventricular septal defect, and a giant omphalocele were noted. He had short stature. He was diagnosed in childhood with autism and pervasive developmental disorder and had significant behavioral issues with anxiety and panic attacks. His parents were unaffected.
Inheritance
The transmission pattern of Teebi hypertelorism syndrome in several reported families supports autosomal dominant inheritance (e.g., Teebi, 1987; Koenig, 2003; Han et al., 2006).
Molecular Genetics
Using whole-exome sequencing, Bhoj et al. (2015) identified heterozygosity for a deletion (614140.0004) and a missense mutation (E420D; 614140.0005) in the SPECC1L gene in 2 unrelated families with features consistent with Teebi hypertelorism syndrome. Both mutations were confirmed by Sanger sequencing. The family with the missense mutation, in which a mother and son were affected, had previously been reported by Hoffman et al. (2007) as having a distinct syndrome resembling Teebi hypertelorism and Aarskog syndromes. The deletion mutation occurred de novo.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Prominent forehead \- Long philtrum Ears \- Preauricular pits Eyes \- Hypertelorism \- Ptosis \- Upslanting palpebral fissures \- Arched eyebrows Nose \- Depressed nasal bridge \- Short nose Mouth \- Thin vermillion of upper lip Teeth \- Natal teeth \- Dental crowding \- Enamel defects CARDIOVASCULAR Heart \- Ventricular septal defect \- Atrial septal defect RESPIRATORY Lung \- Pulmonary hypoplasia secondary to omphalocele ABDOMEN External Features \- Omphalocele \- Protruding umbilicus GENITOURINARY External Genitalia (Male) \- Shawl scrotum Internal Genitalia (Female) \- Bicornuate uterus SKELETAL Skull \- Craniosynostosis Spine \- Hypersegmented lumbar vertebrae Hands \- Small hands NEUROLOGIC Central Nervous System \- Pervasive developmental disorder (in 1 patient) Behavioral Psychiatric Manifestations \- Anxiety (in 1 patient) \- Panic attacks (in 1 patient) PRENATAL MANIFESTATIONS Placenta & Umbilical Cord \- Two-vessel cord MISCELLANEOUS \- A mother and son and another boy have been described with SPECC1L mutations MOLECULAR BASIS \- Caused by mutation in the sperm antigen with calponin homology and coiled-coil domains 1-like gene (SPECC1L, 614140.0004 ) ▲ 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
| HYPERTELORISM, TEEBI TYPE | c0796179 | 2,313 | omim | https://www.omim.org/entry/145420 | 2019-09-22T16:39:51 | {"mesh": ["C536951"], "omim": ["145420"], "orphanet": ["1519"], "synonyms": ["Alternative titles", "Teebi hypertelorism syndrome", "Teebi syndrome", "BRACHYCEPHALOFRONTONASAL DYSPLASIA", "Brachycephalofrontonasal dysplasia", "Craniofrontonasal dysplasia, Teebi type"]} |
Loeys-Dietz syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, and blood vessels.
There are five types of Loeys-Dietz syndrome, labelled types I through V, which are distinguished by their genetic cause. Regardless of the type, signs and symptoms of Loeys-Dietz syndrome can become apparent anytime from childhood through adulthood, and the severity is variable.
Loeys-Dietz syndrome is characterized by enlargement of the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection). People with Loeys-Dietz syndrome can also have aneurysms or dissections in arteries throughout the body and have arteries with abnormal twists and turns (arterial tortuosity).
Individuals with Loeys-Dietz syndrome often have skeletal problems including premature fusion of the skull bones (craniosynostosis), an abnormal side-to-side curvature of the spine (scoliosis), either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum), an inward- and upward-turning foot (clubfoot), flat feet (pes planus), or elongated limbs with joint deformities called contractures that restrict the movement of certain joints. A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia). In individuals with Loeys-Dietz syndrome, dural ectasia typically does not cause health problems. Malformation or instability of the spinal bones (vertebrae) in the neck is a common feature of Loeys-Dietz syndrome and can lead to injuries to the spinal cord. Some affected individuals have joint inflammation (osteoarthritis) that commonly affects the knees and the joints of the hands, wrists, and spine.
People with Loeys-Dietz syndrome may bruise easily and develop abnormal scars after wound healing. The skin is frequently described as translucent, often with stretch marks (striae) and visible underlying veins. Some individuals with Loeys-Dietz syndrome develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax) or a protrusion of organs through gaps in muscles (hernias). Other characteristic features include widely spaced eyes (hypertelorism), eyes that do not point in the same direction (strabismus), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and an opening in the roof of the mouth (cleft palate).
Individuals with Loeys-Dietz syndrome frequently develop immune system-related problems such as food allergies, asthma, or inflammatory disorders such as eczema or inflammatory bowel disease.
## Frequency
The prevalence of Loeys-Dietz syndrome is unknown. Loeys-Dietz syndrome types I and II appear to be the most common forms.
## Causes
The five types of Loeys-Dietz syndrome are distinguished by their genetic cause: TGFBR1 gene mutations cause type I, TGFBR2 gene mutations cause type II, SMAD3 gene mutations cause type III, TGFB2 gene mutations cause type IV, and TGFB3 gene mutations cause type V. These five genes play roles in a cell signaling pathway called the transforming growth factor beta (TGF-β) pathway, which directs the functions of the body's cells during growth and development. This pathway also regulates the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells and is important for tissue strength and repair.
Mutations in the TGFBR1, TGFBR2, SMAD3, TGFB2, or TGFB3 gene result in the production of a protein with reduced function. Even though the protein is less active, signaling within the TGF-β pathway occurs at an even greater intensity than normal in tissues throughout the body. Researchers speculate that the activity of other proteins in this signaling pathway is increased to compensate for the protein whose function is reduced; however, the exact mechanism responsible for the increase in signaling is unclear. The overactive TGF-β pathway disrupts the development of the extracellular matrix and various body systems, leading to the signs and symptoms of Loeys-Dietz syndrome.
### Learn more about the genes associated with Loeys-Dietz syndrome
* SMAD3
* TGFB2
* TGFB3
* TGFBR1
* TGFBR2
## Inheritance Pattern
Loeys-Dietz syndrome has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
In about 75 percent of cases, this disorder results from a new gene mutation and occurs in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Loeys-Dietz syndrome | c4551955 | 2,314 | medlineplus | https://medlineplus.gov/genetics/condition/loeys-dietz-syndrome/ | 2021-01-27T08:24:59 | {"gard": ["10788"], "mesh": ["D055947"], "omim": ["609192", "610168", "613795", "614816", "615582"], "synonyms": []} |
## Summary
### Clinical characteristics.
LTBP4-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow visceral diverticula (e.g., intestine, bladder). Other manifestations can include diaphragmatic hernia, congenital heart disease, intestinal malrotation, and ectopic kidneys. Of the 17 affected individuals (from 13 families) reported to date, cutis laxa was evident from birth in most and pulmonary emphysema was present in all. Pulmonary emphysema is clinically evident during the first months of life, is often severe, and is the most common cause of death. Bladder diverticula and hydronephrosis are common.
### Diagnosis/testing.
The diagnosis of LTBP4-related cutis laxa is established in a proband with cutis laxa and biallelic pathogenic variants in LTBP4.
### Management.
Treatment of manifestations: Treatment is largely symptomatic and may include: routine treatment of pulmonary emphysema (inhaled corticosteroids, atropine, and selective β2-adrenergic bronchodilation, and supplemental oxygen as needed) and gastroesophageal reflux; education on complete bladder emptying when voiding; and treatment of clinically relevant pulmonary artery stenosis and pulmonary hypertension.
Prevention of secondary complications: Routine immunizations against respiratory infections.
Surveillance: Routine assessment of pulmonary function and oxygenation and repeat imaging of the GI tract, urinary tract, and cardiovascular system.
Agents/circumstances to avoid: Positive pressure ventilation (unless needed to treat life-threatening conditions); isometric exercise and contact sports or activities that increase the risk for blunt abdominal trauma and/or joint injury or pain; exposure to people with respiratory infections.
### Genetic counseling.
LTBP4-related cutis laxa is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing or preimplantation genetic testing for pregnancies at increased risk are possible if the LTBP4 pathogenic variants in the family are known.
## Diagnosis
No formal clinical diagnostic criteria have been established for LTBP4-related cutis laxa.
### Suggestive Findings
LTBP4-related cutis laxa should be suspected in individuals with loose redundant skin folds (cutis laxa) and various internal organ involvement including pulmonary emphysema and gastrointestinal and/or urinary tract diverticula.
The following major clinical findings and the rest of this GeneReview are based on the three reports published on LTBP4-related cutis laxa [Urban et al 2009, Callewaert et al 2013, Su et al 2015].
Skin
* Loose redundant skin folds, mainly on the trunk and limbs with variable involvement of the facial skin resulting in a droopy and puffy face giving a prematurely aged appearance. Rarely, the skin can be mainly hyperextensible instead of lax.
* Thin skin with prominent veins
Pulmonary
* Emphysema: variable but is mostly congenital or early-onset and progressive; may clinically manifest as respiratory distress or hypoxia; may be evident on routine x-rays or lung CT
* Laryngomalacia, tracheomalacia, bronchomalacia
* Bronchiolitis: may be severe and result in progression of emphysematous lesions
Gastrointestinal
* Diverticula throughout the gastrointestinal tract
* Gastrointestinal tract dilatations
* Elongated gastrointestinal tract resulting in tortuosity
* Perforation of the stomach or intestine
* Gastroesophageal reflux
* Rectal prolapse
* Pyloric stenosis
Genitourinary
* Bladder diverticula and rupture
* Hydronephrosis
* Urinary tract infections (secondary to anatomic abnormalities of the urinary tract)
Cardiovascular
* Peripheral pulmonary artery stenosis
* Atrial septal defects and atrial septal aneurysms
* Cardiac valve insufficiency (mitral, tricuspid, aortic)
* Pulmonary and aortic valve stenosis
* Pulmonary hypertension
Craniofacial
* Sagging skin with prominent sagging cheeks
* Sparse hair, especially temporally
* Sloping forehead
* Narrow forehead
* Periorbital fullness
* Epicanthus
* Depressed nasal bridge
* Anteverted nares
* Long philtrum
* Micrognathia
* Large ears
Other
* Inguinal and umbilical hernias
* Sliding and diaphragmatic hernias or diaphragmatic eventration
* Muscular hypotonia
* Joint laxity
### Establishing the Diagnosis
The diagnosis of LTBP4-related cutis laxa is established in a proband with cutis laxa and biallelic pathogenic variants in LTBP4 (see Table 1).
It is appropriate to perform molecular analysis of LTBP4 in individuals with all of the following:
* Cutis laxa or hyperextensible skin
* Pulmonary emphysema
* Gastrointestinal and/or bladder diverticula
Molecular genetic testing approaches can include:
* Sequence analysis of LTBP4 followed by deletion/duplication analysis if only one or no pathogenic variant is found. Note: To date, no large intragenic deletions have been reported in affected individuals.
* Use of a multigene panel that includes LTBP4 and other genes of interest (see Differential Diagnosis). Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
### Table 1.
Molecular Genetic Testing Used in LTBP4-Related Cutis Laxa
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
LTBP4Sequence analysis 317/17 4
Gene-targeted deletion/duplication analysis 4Unknown; none reported to date
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Urban et al [2009], Callewaert et al [2013], Su et al [2015]
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.
## Clinical Characteristics
## Differential Diagnosis
Disorders to consider in the differential diagnosis of LTBP4-related cutis laxa are summarized in Table 2 and discussed below.
### Table 2.
Disorders to Consider in the Differential Diagnosis of LTBP4-Related Cutis Laxa
View in own window
FindingDisorder
ARCL1AARCL1BARCL1CADCLARCL2A
ARCL2BARCL3A
ARCL3BProgeroid
ADCLXLCLATS
Gene(s)FBLN5EFEMP2LTBP4ELNATP6V0A2
PYCR1ALDH18A1
PYCR1ALDH18A1ATP7ASLC2A10
SkinRedundantHyper-
extensible >
redundantRedundantRedundant >
hyper-
extensibleWrinkled >
redundantWrinkled, thinWrinkled, thinWrinkledHyper-
extensible >
redundant
Emphysema+++++++++NoNoNoNoNo
CardiovascularArterial stenosesArterial tortuosity/
aneurysmsArterial stenosis, septal defectsARD-Arterial stenoses, ICA malformedICA
tortuosityICA
tortuosityArterial
tortuosity
Hiatal/
diaphragmatic
hernias+++++++NoNo+++
Bladder
diverticula++++++++NoNo++++
GI diverticulaNoNo+++NoNoNoNoNoNo
IUGRNoNo+No+++++++NoNo
Postnatal
growth delay+++++No+++++++++No
Congenital hip
dislocationNo+NoNo+++++++NoNo
Osteoporosis,
bone fragilityNo++NoNoN/AN/AN/A++No
ScoliosisNo+NoNo++++++++++
Delayed anterior
fontanelle closureNoNo+No+++++++++No
MicrocephalyNoNoNoNo+++++++++No
Intellectual
disabilityNoNoNoNo+++++++++No
Brain
malformationsNoNoNoNoCobblestone gyri (ATP6V0A2)
CCA (PYCR1)CCA+NoNo
Athetoid
movementsNoNoNoNoNo++++NoNo
Corneal
opacification /
cataractNoNoNoNoNo++++++NoNo
OtherGlycosylation
defectsBrisk
reflexesBony exostoses
(>occipital)
Features characteristic for the indicated disorder are shown underlined.
\+ = rare case reports; ++ = multiple case reports; +++ = common finding; ADCL = autosomal dominant cutis laxa; ARCL = autosomal recessive cutis laxa; ARD = aortic root dilatation; ATS = arterial tortuosity syndrome; CCA = corpus callosum agenesis; CV = cardiovascular; ICA = intracranial arteries; IUGR = intrauterine growth restriction; No = not present; XLCL = X-linked cutis laxa
Autosomal recessive cutis laxa type 1A (ARCL1A, FBLN5-related cutis laxa) is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow visceral diverticula (e.g., intestine, bladder). Occasionally, supravalvular aortic stenosis is observed. Considerable overlap exists between FBLN5\- and LTBP4-related cutis laxa and the two entities are difficult to distinguish from each other purely on a clinical basis. In FBLN5-related cutis laxa, the skin features may be more pronounced. In LTBP-related cutis laxa, supravalvular aortic stenosis has not yet been observed while bladder and gastrointestinal diverticula as well as rectal prolapse are more frequent.
Autosomal recessive cutis laxa type 1B (ARCL1B, EFEMP2 (FBLN4)-related cutis laxa) is characterized by cutis laxa and systemic involvement, most commonly arterial tortuosity, aneurysms and stenosis; retrognathia; joint laxity; and arachnodactyly. The severe arterial tortuosity seen in EFEMP2-related cutis laxa is absent in LTBP4-related cutis laxa.
Autosomal dominant cutis laxa type 1 (ADCL1) presents with generalized cutis laxa of variable severity. Aortic root dilatation and emphysema may occur and are currently only reported in adults, unlike the severe emphysema seen in LTBP4-related cutis laxa. ADCL1 is caused by ELN pathogenic variants that result in an elongated protein [Szabo et al 2006, Callewaert et al 2011, Hadj-Rabia et al 2013].
Autosomal recessive cutis laxa type 2A (ARCL2A, ATP6V0A2-related cutis laxa). The phenotypic spectrum of ATP6V0A2-related cutis laxa includes Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end. Affected individuals have furrowing and premature wrinkling of the skin of the entire body that improves with time. In most (not all) affected individuals, microcephaly and cortical and cerebellar malformations are present and are associated with variable developmental delay, seizures, and/or neurologic regression [Kornak et al 2008, Fischer et al 2012].
Autosomal recessive cutis laxa type 2B and 3B (ARCL2B and ARCL3B) (OMIM 612940, 614438). Although individuals with ARCL2B may have findings similar to ARCL2A, they often have a more progeroid appearance with a triangular face and corpus callosum agenesis. Patients who additionally have corneal clouding due to ruptures in Descemet’s membrane or cataracts are considered to have ARCL3B (de Barsy syndrome B) [Reversade et al 2009, Dimopoulou et al 2013]. ARCL2B and ARCL3B are caused by mutation of PYCR1.
Autosomal recessive cutis laxa type 3A (ARCL3A, de Barsy syndrome A) (OMIM 219150) is similar to ARCL3B, but is usually situated at the most severe end of the type 3 recessive cutis laxa spectrum with severe IUGR, a progeroid appearance with a thin skin and visible veins, adducted thumbs, and corneal clouding and/or cataract. In addition, patients with ARCL3A can show choreoathetoid movements and arterial involvement, including aortic stenosis and intracranial aneurysms [Zampatti et al 2012, Fischer et al 2014]. ARCL3A is caused by mutation of ALDH18A1.
Central nervous system and ocular anomalies in the absence of severe emphysema distinguish these disorders from LTBP4-related cutis laxa.
Geroderma osteodysplasticum (GO) (OMIM 231070), an autosomal recessive disorder that resembles ARCL2, has some distinct craniofacial characteristics and severe skeletal manifestations (osteopenia and fractures). Lipodystrophy and periodontal disease may occur. Emphysema is usually absent. Both mutation of GORAB [Hennies et al 2008] and PYCR1 [Yildirim et al 2011] have been described.
Occipital horn syndrome (OHS) (sometimes referred to as X-linked cutis laxa [XLCL]) is characterized by "occipital horns," distinctive wedge-shaped exostoses at the sites of attachment of the trapezius muscle and the sternocleidomastoid muscle to the occipital bone. Individuals with OHS also have lax skin and joints, bladder diverticula, inguinal hernias, and vascular tortuosity. Cutis laxa in OHS is often less severe and mostly involves wrinkling of the dorsum of the hands and feet. OHS is caused by mutation of ATP7A (encoding a copper transporter).
The skeletal abnormalities and abnormalities of the hair shaft (pili torti) seen in OHS and the absence of severe emphysema distinguish it from LTBP4-related cutis laxa.
Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by:
* Severe and widespread arterial tortuosity of the aorta and middle-sized arteries (with an increased risk of aneurysms and dissections) and focal and widespread stenosis which can involve the aorta and/or pulmonary arteries. In addition, large veins may be dilated and valvular regurgitation and mitral valve prolapse can occur.
* Craniofacial involvement with characteristic facies and high palate with dental crowding;
* Soft/doughy skin and other evidence of a generalized connective tissue disorder including skeletal findings (scoliosis, pectus excavatum/carinatum, joint laxity, knee/elbow contractures, arachnodactyly, camptodactyly); inguinal/abdominal wall hernia; sliding hiatal or diaphragmatic hernia; hypotonia; and ocular involvement (myopia, keratoconus).
ATS is caused by mutation of SLC2A10. The absence of severe lung involvement and the presence of arterial tortuosity distinguish ATS from ARCL1C.
Macrocephaly, alopecia, cutis laxa, scoliosis (MACS) syndrome (also known as RIN2 syndrome) (OMIM 613075) is an autosomal recessive disorder that includes the eponymous clinical manifestations as well as progressive facial coarsening, gingival hyperplasia, and skin and joint laxity. The skin phenotype has been described variably as cutis laxa [Basel-Vanagaite et al 2009] or hyperextensible [Syx et al 2010]. RIN2 encodes a Ras and Rab interactor with guanine nucleotide exchange factor activity involved in endocytosis.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with LTBP4-related cutis laxa, the following evaluations are recommended:
* Assessment of lung function, including oxygen saturation, spirometry, lung volumes, and diffusion capacity
* Chest x-ray or high-resolution CT scan
* Ultrasound examination of the genitourinary tract
* Bladder ultrasound examination to diagnose multiple bladder diverticula
* Echocardiography
* Physiotherapeutic evaluation (hypotonia, hyperlaxity)
* Consultation with a clinical geneticist and/or genetic counselor
On clinical indication:
* Bronchoscopy
* Visualization of the gastrointestinal tract by gastrographin ingestion or enema
* Pulmonary vessel angiogram
* If necessary, bladder ultrasound can be complemented with a voiding cystoureterogram. Due to the potential presence of urethral diverticula, catheterization should be done carefully. Intravenous pyelogram may be an alternative.
### Treatment of Manifestations
Experience in treating patients with LTBP4-related cutis laxa is very limited. Treatment is largely symptomatic. A reasonable approach to treatment could include the following.
Pulmonary
* Symptomatic treatment of pulmonary emphysema with inhaled corticosteroids, atropine, and selective β2-adrenergic bronchodilation
* Oxygen supplementation if necessary
Gastrointestinal
* Medical treatment of gastroesophageal reflux to reduce discomfort and reactive bronchospasms
* Feeding of mother’s milk in infants to maximize passive immunization
* Dietary advice, sufficient fluid intake and, if necessary, osmotic laxatives to avoid chronic constipation
Genitourinary
* Education on complete bladder emptying when voiding
* Antibiotic prophylaxis in case of incomplete voiding and recurrent urinary tract infections
* Pelvic floor strengthening by physical therapy may help to prevent prolapse of pelvic organs
* Consideration of artificial bladder implantation (performed in 1 patient)
Cardiovascular
* Care by a (pediatric) cardiologist with experience in connective tissue pathology
* Treatment of clinically relevant pulmonary artery stenosis (preferably by catheterization which is minimally invasive and needs a shorter period of anesthesia)
* Medical treatment of pulmonary hypertension (e.g., by sildenafil)
Other
* Surgical treatment of congenital diaphragmatic hernia or severe hiatal hernia
* Caution in surgical treatment of cutis laxa and inguinal or umbilical hernia, as the risk of recurrence is likely to be high (i.e., similar to that observed in other cutis laxa syndromes) and mechanical ventilation used during the procedure may aggravate pulmonary emphysema
* Physical therapy for muscle strength and joint stability
* Psychosocial support
### Prevention of Secondary Complications
Immunize against respiratory infections (influenza, Streptococcus pneumonia, Haemophilus influenza).
Passive immunization for respiratory syncytial virus (RSV) with palivizumab may be considered during the RSV season.
### Surveillance
The following are appropriate:
* Routine assessment of pulmonary function and oxygenation, at least yearly, or more frequently if indicated clinically
* Repeat imaging of:
* Gastrointestinal tract
* Urinary tract
* Cardiovascular system
### Agents/Circumstances to Avoid
Avoid the following:
* Positive pressure ventilation unless needed to treat life-threatening conditions
* Isometric exercise and contact sports or activities that increase the risk for blunt abdominal trauma and/or joint injury or pain
* People with respiratory infections
* Sunbathing or tanning in order to preserve any residual skin elasticity
* Smoking, which can result in rapid, severe loss of lung function in persons with LTBP4-related cutis laxa
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. In one family, recurrent spontaneous abortions have been noted.
### Pregnancy Management
Affected mother. To date pregnancy has been observed in one affected female with an unaffected fetus. The pregnancy was uneventful, but delivery was induced because of elevated maternal blood pressure. Delivery was vaginal with normal healing and no signs of prolapse. Two years after delivery both the mother and her son were doing well.
Despite evidence for the possibility of relatively normal pregnancy, a risk of aggravation of cardiopulmonary manifestations, and increased risk of both uterine rupture and exacerbation of pelvic floor/organ insufficiency including uterine, bladder, and rectal prolapse cannot be excluded based on this single case. Therefore, it is recommended that follow up of pregnancy and the postnatal period be done in a high-risk obstetric care unit with experience in connective tissue disorders.
Affected fetus
* Major complications, such as preterm premature rupture of membranes, have not been reported during pregnancy with affected fetuses.
* Polyhydramnios has been described in two instances in association with esophageal tortuosity or diverticulosis [Callewaert et al 2013].
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| LTBP4-Related Cutis Laxa | None | 2,315 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK343782/ | 2021-01-18T21:15:27 | {"synonyms": ["Autosomal Recessive Cutis Laxa Type 1C (ARCL1C)", "Urban-Rifkin-Davis Syndrome (URDS)"]} |
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The term dysphrenia was coined by the German medical specialist Karl Kahlbaum to designate a clinical picture in 19th-century psychiatry. Today the concept is still used in the western world as a lay generic synonym for mental disorder in adults, and as a term to describe different cognitive/verbal/behavioral deficits in children and adolescents. It is also used in the People's Republic of China, controversially, to identify a local medical diagnostic category. A number of followers of Falun Gong and other social movements considered insurrectionary by the regime are said to have been diagnosed with dysphrenia.
## References[edit]
* Chouinard G, Jones BD. Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics. Am J Psychiatry. 1980 Jan;137(1):16-21.
* Fink M, Taylor MA. Catatonia. A History. In: Catatonia. A Clinician’s Guide to Diagnosis and Treatment. Cambridge University Press, Cambridge, 2003. ISBN 0-521-82226-2
* Forrest DV, Fahn S. Tardive dysphrenia and subjective akathisia. J Clin Psychiatry. 1979 Apr;40(4):206. PMID 33972
* Frota LH. Partial Agonists in the Schizophrenia Armamentarium. Tardive Dysphrenia: The newest challenge to the last generation atypical antipsychotics drugs? J Bras Psiquiatr 2003; Vol 52 Supl 1;14-24.
* Lehmann HE, Ban TA. The History of Psychopharmacology of Schizophrenia. Canadian Journal of Psychiatry 1997; 42:152-62.
This abnormal psychology–related article is a stub. You can help Wikipedia by expanding it.
* v
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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
| Dysphrenia | None | 2,316 | wikipedia | https://en.wikipedia.org/wiki/Dysphrenia | 2021-01-18T19:04:04 | {"wikidata": ["Q3710022"]} |
A number sign (#) is used with this entry because of evidence that rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp (EPRPDC) is caused by compound heterozygous mutation in the TBC1D24 gene (613577) on chromosome 16p13.
Description
Rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp (EPRPDC) is an autosomal recessive neurologic disorder characterized by onset of focal seizures in infancy and exercise-induced dystonia in childhood. Features usually include involuntary movements, including facial movements, and difficulties with fine motor skills of the hand. Seizures often respond to medication and remit with age; the dystonia tends to persist (summary by Luthy et al., 2019).
Clinical Features
In 3 members from the same generation of a consanguineous Italian family, Guerrini et al. (1999) described a syndrome comprising rolandic epilepsy (RE; see 117100), paroxysmal exercise-induced dystonia (PED), and writer's cramp (WC). Onset was in infancy, with partial seizures that were often hemifacial, and paroxysmal dystonia of the neck, trunk, or limbs associated with exercise. Both the seizures and the paroxysmal dystonia had an age-related expression that peaked during childhood. Horizontal nystagmus was also present. EEG showed rolandic sharp waves or spikes.
Luthy et al. (2019) provided follow-up of the Italian patients reported by Guerrini et al. (1999), who were 31, 42, and 43 at the time of the second report. Focal motor seizures never reoccurred after ages 16, 18, and 22 under treatment with carbamazepine or oxcarbazepine; however, exercise-induced dystonia was still present in 2 of the patients, although the frequency of episodes had decreased. All 3 patients still had nystagmus and postural tremor of the hands. Brain imaging was normal.
Luthy et al. (2019) also identified 3 unrelated patients with a similar disorder. They had onset of focal motor seizures, consistent with rolandic seizures, in the first year of life, followed by onset of exercise-induced dystonia between 2 and 4 years of age. Features included clonic or myoclonic jerks of the hands and face, drooling, dysarthria, dysphagia, difficulty with fine motor movements of the hands, and involuntary movements. Symptoms were often exacerbated by fatigue, fever, or excitement. EEG in 2 patients showed frontotemporal focal discharges. Seizures remitted by age 9 years in 1 patient, but still occurred at ages 8 and 13 years in the other 2 patients. Two patients had postural hand tremor; all had normal brain imaging. Two of the patients were of Han Chinese descent.
Inheritance
The transmission pattern of EPRPDC in the family reported by Guerrini et al. (1999) was consistent with autosomal recessive inheritance.
Mapping
In a family with RE-PED-WC, Guerrini et al. (1999) found linkage to a 6-cM region on chromosome 16p12-p11.2 between markers D16S3133 and D16S3131 (maximum lod score of 3.68). The authors noted that the disorder showed phenotypic similarities to autosomal dominant infantile convulsions and paroxysmal choreoathetosis syndrome (ICCA; 602066), which had been mapped to the same region.
Molecular Genetics
In 3 members of a consanguineous Italian family with EPRPDC, Luthy et al. (2019) identified compound heterozygous missense mutations in the TBC1D24 gene (G501R, 613577.0015 and R360H, 613577.0016). The mutations, which were found by sequencing of the critical region identified by linkage analysis (Guerrini et al., 1999), segregated with the disorder in the family. Three additional patients, including 2 unrelated patients of Han Chinese origin, with sporadic occurrence of the disorder were found to carry compound heterozygous mutations (see, e.g., 613577.0017 and 613577.0018) through whole-exome sequencing. All the patients had biallelic mutations that could be described as hypomorphic mutations affecting the TBC domain, which is important for the regulation of vesicular membrane trafficking at synapses, or a mutation with a mild effect on protein function (R360H), coupled with missense mutations that severely affect the TLDc domain, which is the catalytic domain and thought to be involved in oxidative stress resistance. Studies of patient cells were not performed, but detailed structural analysis predicted that the mutations may have variable destabilizing effects on the protein. In vivo studies in Drosophila demonstrated that the G501R TLDc mutation caused activity-induced locomotion and synaptic vesicle trafficking defects, while R360H was comparatively benign. The neuronal phenotypes of the G501R mutation were consistent with exacerbated oxidative stress sensitivity, which could be rescued by treatment with antioxidants that restored synaptic vesicle trafficking levels and sustained behavioral activity. The authors suggested that the TBC1D24 TLDc domain is a reactive oxygen species sensor mediating synaptic vesicle trafficking rates that, when dysfunctional, causes a movement disorder in patients and flies.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Abnormal facial movements Eyes \- Nystagmus, horizontal NEUROLOGIC Central Nervous System \- Seizures, focal, partial, often hemifacial \- Seizures, generalized, may occur \- Paroxysmal dystonia, exercise-induced \- Writer's cramp \- Difficulty with fine motor skills \- Tremor \- Dysarthria \- Nystagmus, horizontal \- Myoclonic jerks \- Rolandic sharp waves and spikes seen on EEG \- Prolonged somatosensory evoked potentials (SEPs) MISCELLANEOUS \- Onset in infancy (1-2 years) \- Seizures and dystonia peak during childhood \- Seizures tend to remit with age \- Features may be exacerbated by fatigue or stress MOLECULAR BASIS \- Caused by mutation in the TBC1 domain family, member 24 gene (TBC1D24, 613577.0015 ) ▲ 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
| EPILEPSY, ROLANDIC, WITH PAROXYSMAL EXERCISE-INDUCED DYSTONIA AND WRITER'S CRAMP | c1842531 | 2,317 | omim | https://www.omim.org/entry/608105 | 2019-09-22T16:08:15 | {"mesh": ["C535499"], "omim": ["608105"], "orphanet": ["163727"], "synonyms": ["Alternative titles", "RE-PED-WC"]} |
A group of spinocerebellar ataxias (SCAs) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement.
## Epidemiology
The overall prevalence of SCAs is 1/33,000-1/50,000. The prevalence of ADCA (all types) is estimated at 1/37,000 worldwide. The most common ADCA type I is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations.
## Clinical description
Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations that include spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric disorders, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated.
## Etiology
To date, 27 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12- SCA14, SCA15/SCA16, SCA17- SCA23, SCA25, SCA27, SCA28, SCA32, SCA34- SCA37, autosomal dominant cerebellar ataxia, deafness and narcolepsy, and dentatorubral pallidoluysian atrophy (DRPLA) (see these terms). ADCA type I can be further divided based on the proposed pathogenetic mechanism into 3 subclasses. Subclass 1 includes ADCA type I caused by CAG repeat expansions such as in SCA1-SCA3, SCA17 and DRPLA. Subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12, as well as hexanucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA36. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/SCA16, SCA27- SCA28 and SCA35.
## Diagnostic methods
Diagnosis is based on clinical history, physical examination, genetic molecular testing, and exclusion of other diseases.
## Differential diagnosis
Differential diagnosis is broad and includes secondary ataxias caused by drug or toxic effects, nutritional deficiencies, endocrinopathies, infections and post-infection states, structural abnormalities, paraneoplastic conditions and certain neurodegenerative disorders.
## Antenatal diagnosis
Prenatal diagnosis is possible in families with a known disease causing mutation.
## Genetic counseling
Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics.
## Management and treatment
There are currently no known effective treatments to modify disease progression. Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential.
## Prognosis
Prognosis is variable depending on the type of SCA and even among kindreds.
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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
| Autosomal dominant cerebellar ataxia type I | None | 2,318 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=94145 | 2021-01-23T18:26:54 | {"icd-10": ["G11.8"], "synonyms": ["ADCA1", "ADCAI", "Autosomal dominant cerebellar ataxia type 1", "Cerebellar plus syndrome"]} |
A rare genetic gynecological tumor characterized by early onset breast cancer in association with a germline mutation. Tumors arising in carriers of BRCA1 and BRCA2 mutations differ morphologically and genetically from each other, as well as from sporadic breast cancers. Most BRCA1-associated tumors are invasive ductal adenocarcinomas of no special type, typically of higher grade than sporadic tumors, and more often negative for hormone receptors. In addition, more cases with features of typical or atypical medullary carcinoma are seen in these patients. Likewise, BRCA2-associated tumors tend to be of higher grade than sporadic ones, although their phenotype is similar. They show a low frequency of HER-2 expression.
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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
| Hereditary breast cancer | c0346153 | 2,319 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=227535 | 2021-01-23T18:59:35 | {"mesh": ["C562840"], "omim": ["114480", "604370", "612555", "613399"], "umls": ["C0346153"], "icd-10": ["C50.0", "C50.1", "C50.2", "C50.3", "C50.4", "C50.5", "C50.6", "C50.8"], "synonyms": ["Familial breast cancer", "Familial breast carcinoma", "Hereditary breast carcinoma"]} |
The most common type of cancers affecting the animal's nose are carcinomas and sarcomas, both of which are locally invasive. The most common sites for metastasis are the lymph nodes and the lungs, but can also include other organs.
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
Signs vary but may include bleeding from the nose, nasal discharge, facial deformity from bone erosion and tumor growth, sneezing, or difficulty breathing.
## Diagnosis[edit]
Standard X-rays are still acceptable and readily accessible imaging tools but their resolution and level of anatomical detail are not as good as for computed tomography (CT) scan. In order to definitively confirm cancer in the nasal cavity, a tissue biopsy should be obtained.[1]
## Treatment[edit]
Radiation therapy has become the preferred treatment. Its advantage is that it treats the entire nasal cavity together with the affected bone and has shown the greatest improvement in survival. The radiation therapy is typically delivered in 10-18 treatment sessions over the course of 2–4 weeks.
Radiation therapy has a multitude of accompanying side effects and should be recommended on a case-by-case basis. Dogs in which nose bleeds are observed have an average life expectancy of 88 days. In instances where nosebleeds are not seen, the prognosis is slightly less grim. On average, a dog with nasal cancer has a life expectancy of 95 days.
## References[edit]
1. ^ Withrow SJ, MacEwen EG, eds. (2001). Small Animal Clinical Oncology (3rd ed.). W.B. Saunders Company.
## External links[edit]
* Nasal Cavity Cancer in Cats and Dogs from Pet Cancer Center
* Nasal Planum Cancer in Cats and Dogs from Pet Cancer Center'
* Tumors of the Nose from Merck Veterinary Manual
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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
| Nose cancer in cats and dogs | None | 2,320 | wikipedia | https://en.wikipedia.org/wiki/Nose_cancer_in_cats_and_dogs | 2021-01-18T18:28:07 | {"wikidata": ["Q7061746"]} |
A number sign (#) is used with this entry because of evidence that autosomal dominant osteopetrosis-1 (OPTA1) is caused by heterozygous mutation in the LRP5 gene (603506) on chromosome 11q13.
Description
The osteopetroses are a heterogeneous group of genetic disorders characterized by increased bone density due to impaired bone resorption by osteoclasts. Autosomal dominant osteopetrosis-1 is characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate (summary by Van Hul et al., 2002).
### Genetic Heterogeneity of Autosomal Dominant Osteopetrosis
Autosomal dominant osteopetrosis-2 (OPTA2; 166600) is caused by mutation in the CLCN7 gene (602727) on chromosome 16p13. Autosomal dominant osteopetrosis-3 (OPTA3; 618107) is caused by mutation in the PLEKHM1 gene (611466) on chromosome 17q21.
Clinical Features
Andersen and Bollerslev (1987) suggested that autosomal dominant osteopetrosis has 2 distinct radiologic types. Both have universal osteosclerosis, but in type I, the most striking finding is pronounced sclerosis of the cranial vault while the spine is almost unaffected; in type II, the sclerosis of the skull is most pronounced at the base, the vertebrae always have endplate thickening, and in the pelvis, the iliac wings contain convex arcs of sclerotic bone. Age and sex distribution did not differ between the types and each 'bred true' within given families. Bollerslev and Mosekilde (1993) found that bone resorption appears to be defective and bone formation normal in both types of patients. The frequency of fractures is increased in type II patients and normal in type I patients, in whom biomechanical investigations have shown normal or even increased trabecular bone strength.
Bollerslev and Andersen (1988) distinguished type I and type II on the basis of review of the radiographs of 34 patients with autosomal dominant osteopetrosis. Serum phosphate was lower in type I compared to II (P less than 0.01), and serum acid phosphatase was markedly increased in type II (P less than 0.01), suggesting differences between the 2 types in bone mineral metabolism and structural functions of the osteoclasts. No endplate thickening of the spine and no endobones ('bone within a bone') in the pelvis are seen in type I. This type presents as a fully penetrant disorder, compared with type II where the penetrance has been estimated at 60 to 80% (Van Hul et al., 2002).
Mapping
By linkage analysis in 2 Danish families with type I autosomal dominant osteopetrosis, Van Hul et al. (2002) assigned the disease-causing gene to 11q12-q13. A summated maximum lod score of 6.54 was obtained with marker D11S1889, and key recombinants allowed delineation of a candidate region of 6.6 cM.
Molecular Genetics
Van Wesenbeeck et al. (2003) identified a mutation in the LRP5 gene in the Danish families with type I autosomal dominant osteopetrosis used by Van Hul et al. (2002) to map the phenotype to 11q12-q13 (see 603506.0018); they also identified other affected individuals with LRP5 mutations.
Janssens and Van Hul (2002) reviewed the process of bone remodeling and the genetic defects resulting in aberrant bone formation and resorption.
INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Conductive hearing loss SKELETAL \- Diffuse, symmetrical osteosclerosis \- No increased fracture rate Skull \- Pronounced calvarial sclerosis \- Thickened cranial vault Spine \- No 'rugger-jersey spine' \- Variable sclerosis Pelvis \- No endobones NEUROLOGIC Central Nervous System \- Headache LABORATORY ABNORMALITIES \- Normal serum acid phosphatase MISCELLANEOUS \- Allelic to osteoporosis-pseudoglioma syndrome ( 259770 ), van Buchem type 2 ( 607636 ), high bone mass ( 601884 ), autosomal dominant endosteal hyperostosis ( 144750 ) \- Progressive sclerosis with age \- Genetic heterogeneity (see 166600 ) MOLECULAR BASIS \- Caused by mutation in the low-density lipoprotein receptor-related protein 5 gene (LRP5, 603506.0014 ) ▲ 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
| OSTEOPETROSIS, AUTOSOMAL DOMINANT 1 | c1843330 | 2,321 | omim | https://www.omim.org/entry/607634 | 2019-09-22T16:08:56 | {"doid": ["0110937"], "mesh": ["C536056"], "omim": ["607634"], "orphanet": ["2783"], "synonyms": ["Alternative titles", "OSTEOPETROSIS, AUTOSOMAL DOMINANT, TYPE I"]} |
Factor V Leiden thrombophilia
SpecialtyHematology
Factor V Leiden (rs6025 or F5 p.R506Q[1]) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein which normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots.[2] Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans.[3][4][5] It is named after the Dutch city Leiden, where it was first identified in 1994 by Prof R. Bertina under the direction of (and in the laboratory of) Prof P. Reitsma.[6] Despite the increased risk of VTE, people with one copy of this gene have not been found to have shorter lives than the general population.[7]
## Contents
* 1 Signs and symptoms
* 2 Pathophysiology
* 3 Diagnosis
* 4 Management
* 5 Epidemiology
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
The symptoms of factor V Leiden vary among individuals. There are some individuals who have the F5 gene and who never develop thrombosis, while others have recurring thrombosis before the age of 30 years. This variability is influenced by the number of F5 gene mutations a person has, the presence of other gene alterations related to blood clotting, and circumstantial risk factors, such as surgery, use of oral contraceptives and pregnancy.
Symptoms of factor V Leiden include:
* Having a first DVT or PE before 50 years of age.
* Having recurring DVT or PE.
* Having venous thrombosis in unusual sites in the body such as the brain or the liver.
* Having a DVT or PE during or right after pregnancy.
* Having a history of unexplained pregnancy loss in the second or third trimester.
* Having a DVT or PE and a strong family history of venous thromboembolism.
The use of hormones, such as oral contraceptive pills (OCPs) and hormone replacement therapy (HRT), including estrogen and estrogen-like drugs) taken after menopause, increases the risk of developing DVT and PE. Healthy women taking OCPs have a three- to four-fold increased risk of developing a DVT or PE compared with women who do not take OCP. Women with factor V Leiden who take OCPs have about a 35-fold increased risk of developing a DVT or PE compared with women without factor V Leiden and those who do not take OCPs. Likewise, postmenopausal women taking HRT have a two- to three-fold higher risk of developing a DVT or PE than women who do not take HRT, and women with factor V Leiden who take HRT have a 15-fold higher risk. Women with heterozygous factor V Leiden who are making decisions about OCP or HRT use should take these statistics into consideration when weighing the risks and benefits of treatment.
## Pathophysiology[edit]
In the normal pathway, factor V functions as a cofactor to allow factor Xa to activate prothrombin, resulting in the enzyme thrombin. Thrombin in turn cleaves fibrinogen to form fibrin, which polymerizes to form the dense meshwork that makes up the majority of a clot. Activated protein C is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.
SNP: Factor V Leiden
Name(s)Factor V Leiden, Arg506Gln, R506Q, G1691A
GeneFactor V
Chromosome1
External databases
EnsemblHuman SNPView
dbSNP6025
HapMap6025
SNPedia6025
ALFREDSI001216K
Factor V Leiden is an autosomal dominant genetic condition that exhibits incomplete penetrance, i.e. not every person who has the mutation develops the disease. The condition results in a factor V variant that cannot be as easily degraded by activated protein C. The gene that codes the protein is referred to as F5. Mutation of this gene—a single nucleotide polymorphism (SNP) is located in exon 10.[8] As a missense substitution of amino acid R to amino acid Q, it changes the protein's amino acid from arginine to glutamine. Depending on the chosen start the position of the nucleotide variant is either at position 1691 or 1746.[9] It also affects the amino acid position for the variant, which is either 506 or 534. (Together with the general lack of nomenclature standard, this variance means that the SNP can be referred to in several ways, such as G1691A, c.1691G>A, 1691G>A, c.1746G>A, p.Arg534Gln, Arg506Gln, R506Q or rs6025.) Since this amino acid is normally the cleavage site for activated protein C, the mutation prevents efficient inactivation of factor V. When factor V remains active, it facilitates overproduction of thrombin leading to generation of excess fibrin and excess clotting.[10]
The excessive clotting that occurs in this disorder is almost always restricted to the veins, where the clotting may cause a deep vein thrombosis (DVT). If the venous clots break off, these clots can travel through the right side of the heart to the lung where they block a pulmonary blood vessel and cause a pulmonary embolism. It is extremely rare for this disorder to cause the formation of clots in arteries that can lead to stroke or heart attack, though a "mini-stroke", known as a transient ischemic attack, is more common. Given that this disease displays incomplete dominance, those who are homozygous for the mutated allele are at a heightened risk for the events detailed above versus those who are heterozygous for the mutation.[11]
## Diagnosis[edit]
Suspicion of factor V Leiden being the cause for any thrombotic event should be considered in any Caucasian patient below the age of 45, or in any person with a family history of venous thrombosis. There are a few different methods by which this condition can be diagnosed. Most laboratories screen 'at risk' patients with either a snake venom (e.g. dilute Russell's viper venom time) based test or an aPTT based test. In both methods, the time it takes for blood to clot is decreased in the presence of the factor V Leiden mutation. This is done by running two tests simultaneously; one test is run in the presence of activated protein C and the other, in the absence. A ratio is determined based on the two tests and the results signify to the laboratory whether activated protein C is working or not. There is also a genetic test that can be done for this disorder. The mutation (a 1691G→A substitution) removes a cleavage site of the restriction endonuclease MnlI, so PCR, treatment with MnlI, and then DNA electrophoresis will give a diagnosis. Other PCR based assays such as iPLEX can also identify zygosity and frequency of the variant.[citation needed]
## Management[edit]
As there is no cure yet, treatment is focused on prevention of thrombotic complications. Anticoagulants are not routinely recommended for people with factor V Leiden, unless there are additional risk factors present, but are given when such an event occurs.[12][13] A single occurrence of deep vein thrombosis or pulmonary embolism in people with factor V Leiden warrants temporary anticoagulant treatment, but generally not lifelong treatment.[12] In addition, temporary treatment with an anticoagulant such as Heparin may be required during periods of particularly high risk of thrombosis, such as major surgery.[12]
## Epidemiology[edit]
Studies have found that about 5 percent of Caucasians in North America have factor V Leiden. Data have indicated that prevalence of factor V Leiden is greater among Caucasians than minority Americans.[14][15] One study also suggested "that the factor V‐Leiden mutation segregates in populations with significant Caucasian admixture and is rare in genetically distant non‐European groups."[16]
Up to 30 percent of patients who present with deep vein thrombosis (DVT) or pulmonary embolism have this condition. The risk of developing a clot in a blood vessel depends on whether a person inherits one or two copies of the factor V Leiden mutation. Inheriting one copy of the mutation from a parent (heterozygous) increases by fourfold to eightfold the chance of developing a clot. People who inherit two copies of the mutation (homozygous), one from each parent, may have up to 80 times the usual risk of developing this type of blood clot.[17] Considering that the risk of developing an abnormal blood clot averages about 1 in 1,000 per year in the general population, the presence of one copy of the factor V Leiden mutation increases that risk to between 4 in 1,000 to 8 in 1,000. Having two copies of the mutation may raise the risk as high as 80 in 1,000. It is unclear whether these individuals are at increased risk for recurrent venous thrombosis. While only 1 percent of people with factor V Leiden have two copies of the defective gene, these homozygous individuals have a more severe clinical condition. The presence of acquired risk factors for venous thrombosis—including smoking, use of estrogen-containing (combined) forms of hormonal contraception, and recent surgery—further increase the chance that an individual with the factor V Leiden mutation will develop DVT.
Women with factor V Leiden have a substantially increased risk of clotting in pregnancy (and on estrogen-containing birth control pills or hormone replacement) in the form of deep vein thrombosis and pulmonary embolism. They also may have a small increased risk of preeclampsia, may have a small increased risk of low birth weight babies, may have a small increased risk of miscarriage and stillbirth due to either clotting in the placenta, umbilical cord, or the fetus (fetal clotting may depend on whether the baby has inherited the gene) or influences the clotting system may have on placental development.[18] Note that many of these women go through one or more pregnancies with no difficulties, while others may repeatedly have pregnancy complications, and still others may develop clots within weeks of becoming pregnant.[citation needed]
## See also[edit]
* Prothrombin G20210A
## References[edit]
1. ^ Klarin D, Busenkell E, Judy R, Lynch J, Levin M, Haessler J, et al. (November 2019). "Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease" (PDF). Nature Genetics. 51 (11): 1574–1579. doi:10.1038/s41588-019-0519-3. PMC 6858581. PMID 31676865.
2. ^ De Stefano V, Leone G (1995). "Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia". Haematologica. 80 (4): 344–56. PMID 7590506.
3. ^ Ridker PM, Miletich JP, Hennekens CH, Buring JE (1997). "Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening". JAMA. 277 (16): 1305–7. doi:10.1001/jama.277.16.1305. PMID 9109469.
4. ^ Gregg JP, Yamane AJ, Grody WW (December 1997). "Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations". American Journal of Medical Genetics. 73 (3): 334–6. doi:10.1002/(SICI)1096-8628(19971219)73:3<334::AID-AJMG20>3.0.CO;2-J. PMID 9415695.
5. ^ De Stefano V, Chiusolo P, Paciaroni K, Leone G (1998). "Epidemiology of factor V Leiden: clinical implications". Seminars in Thrombosis and Hemostasis. 24 (4): 367–79. doi:10.1055/s-2007-996025. PMID 9763354.
6. ^ Bertina RM, Koeleman BP, Koster T, et al. (May 1994). "Mutation in blood coagulation factor V associated with resistance to activated protein C". Nature. 369 (6475): 64–7. Bibcode:1994Natur.369...64B. doi:10.1038/369064a0. PMID 8164741. S2CID 4314040.
7. ^ Kujovich JL (January 2011). "Factor V Leiden thrombophilia". Genetics in Medicine. 13 (1): 1–16. doi:10.1097/GIM.0b013e3181faa0f2. PMID 21116184.
8. ^ "SNP linked to Gene F5". NCBI.
9. ^ Jennifer Bushwitz; Michael A. Pacanowski & Julie A. Johnson (2006-10-11). "Important Variant Information for F5". PharmGKB. Archived from the original on 2011-07-27. Retrieved 2008-09-10.
10. ^ Juul, Klaus; Tybjærg-Hansen, Anne; Steffensen, Rolf; Kofoed, Steen; Jensen, Gorm; Nordestgaard, Børge Grønne (2002-07-01). "Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses". Blood. 100 (1): 3–10. doi:10.1182/blood-2002-01-0111. ISSN 1528-0020. PMID 12070000.
11. ^ Factor V Leiden Mutation – Homozygous
12. ^ a b c Ornstein, Deborah L.; Cushman, Mary (2003). "Factor V Leiden". Circulation. 107 (15): e94-7. doi:10.1161/01.CIR.0000068167.08920.F1. ISSN 0009-7322. PMID 12707252.
13. ^ Keo, Hong H; Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B. (2015). "Assessing the risk of recurrent venous thromboembolism – a practical approach". Vascular Health and Risk Management. 11: 451–9. doi:10.2147/VHRM.S83718. ISSN 1178-2048. PMC 4544622. PMID 26316770.
14. ^ Ridker, et al. "Ethnic distribution of factor V Leiden in 4047 men and women". Supra.
15. ^ Gregg, et al. "Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations". Supra.
16. ^ Id.
17. ^ What do we know about heredity and factor V Leiden thrombophilia? http://www.genome.gov/15015167#Q5
18. ^ Rodger MA, Paidas M, McLintock C, et al. (August 2008). "Inherited thrombophilia and pregnancy complications revisited". Obstetrics and Gynecology. 112 (2 Pt 1): 320–24. doi:10.1097/AOG.0b013e31817e8acc. PMID 18669729.
## Further reading[edit]
* Herskovits AZ, Lemire SJ, Longtine J, Dorfman DM (November 2008). "Comparison of Russell viper venom-based and activated partial thromboplastin time-based screening assays for resistance to activated protein C". American Journal of Clinical Pathology. 130 (5): 796–804. doi:10.1309/AJCP7YBJ6URTVCWP. PMID 18854273.
* Press RD, Bauer KA, Kujovich JL, Heit JA (November 2002). "Clinical utility of factor V leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders". Archives of Pathology & Laboratory Medicine. 126 (11): 1304–18. doi:10.1043/0003-9985(2002)126<1304:CUOFVL>2.0.CO;2 (inactive 2021-01-15). PMID 12421138.CS1 maint: DOI inactive as of January 2021 (link)
* Hooper WC, De Staercke C (2002). "The relationship between FV Leiden and pulmonary embolism". Respiratory Research. 3 (1): 8. doi:10.1186/rr180. PMC 64819. PMID 11806843.
* Nicolaes GA, Dahlbäck B (April 2002). "Factor V and thrombotic disease: description of a janus-faced protein". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (4): 530–8. doi:10.1161/01.ATV.0000012665.51263.B7. PMID 11950687. S2CID 13215200.
* Andreassi MG, Botto N, Maffei S (2006). "Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening". Clinical Chemistry and Laboratory Medicine. 44 (5): 514–21. doi:10.1515/CCLM.2006.103. PMID 16681418. S2CID 34399027.
* Segers K, Dahlbäck B, Nicolaes GA (September 2007). "Coagulation factor V and thrombophilia: background and mechanisms". Thrombosis and Haemostasis. 98 (3): 530–42. doi:10.1160/th07-02-0150. PMID 17849041. Archived from the original on 2013-02-11.
* Kujovich J; Pagon, RA; Bird, TC; Dolan, CR; Stephens, K (2010) [1999]. "Factor V Leiden Thrombophilia". GeneReviews. PMID 20301542.
* factor+V+Leiden at the US National Library of Medicine Medical Subject Headings (MeSH)
* Kujovich JL, Goodnight SH (2007-02-17). "Factor V Leiden Thrombophilia". GeneReviews. University of Washington, Seattle. Archived from the original on 2008-06-02. Retrieved 2008-06-20.
* Factor V Leiden Thrombophilia Explained - Genome.gov
## External links[edit]
Classification
D
* ICD-10: D68.51
* ICD-9-CM: 289.81
* OMIM: 188055
* MeSH: C095381
* DiseasesDB: 154
* v
* t
* e
Disorders of bleeding and clotting
Coagulation · coagulopathy · Bleeding diathesis
Clotting
By cause
* Clotting factors
* Antithrombin III deficiency
* Protein C deficiency
* Activated protein C resistance
* Protein S deficiency
* Factor V Leiden
* Prothrombin G20210A
* Platelets
* Sticky platelet syndrome
* Thrombocytosis
* Essential thrombocythemia
* DIC
* Purpura fulminans
* Antiphospholipid syndrome
Clots
* Thrombophilia
* Thrombus
* Thrombosis
* Virchow's triad
* Trousseau sign of malignancy
By site
* Deep vein thrombosis
* Bancroft's sign
* Homans sign
* Lisker's sign
* Louvel's sign
* Lowenberg's sign
* Peabody's sign
* Pratt's sign
* Rose's sign
* Pulmonary embolism
* Renal vein thrombosis
Bleeding
By cause
Thrombocytopenia
* Thrombocytopenic purpura: ITP
* Evans syndrome
* TM
* TTP
* Upshaw–Schulman syndrome
* Heparin-induced thrombocytopenia
* May–Hegglin anomaly
Platelet function
* adhesion
* Bernard–Soulier syndrome
* aggregation
* Glanzmann's thrombasthenia
* platelet storage pool deficiency
* Hermansky–Pudlak syndrome
* Gray platelet syndrome
Clotting factor
* Hemophilia
* A/VIII
* B/IX
* C/XI
* von Willebrand disease
* Hypoprothrombinemia/II
* Factor VII deficiency
* Factor X deficiency
* Factor XII deficiency
* Factor XIII deficiency
* Dysfibrinogenemia
* Congenital afibrinogenemia
Signs and symptoms
* Bleeding
* Bruise
* Hematoma
* Petechia
* Purpura
* Nonthrombocytopenic purpura
By site
* head
* Epistaxis
* Hemoptysis
* Intracranial hemorrhage
* Hyphema
* Subconjunctival hemorrhage
* torso
* Hemothorax
* Hemopericardium
* Pulmonary hematoma
* abdomen
* Gastrointestinal bleeding
* Hemobilia
* Hemoperitoneum
* Hematocele
* Hematosalpinx
* joint
* Hemarthrosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Factor V Leiden | c0584960 | 2,322 | wikipedia | https://en.wikipedia.org/wiki/Factor_V_Leiden | 2021-01-18T18:28:22 | {"gard": ["6403"], "mesh": ["C095381"], "icd-9": ["289.81"], "icd-10": ["D68.5"], "wikidata": ["Q185986"]} |
Type III hypersensitivity
Immune complex
SpecialtyImmunology
Type III hypersensitivity occurs when there is accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes. Such reactions may progress to immune complex diseases.
## Contents
* 1 Types
* 2 Signs and symptoms
* 3 See also
* 4 References
* 5 External links
## Types[edit]
Some clinical examples:
Disease Target antigen Main effects
Systemic lupus erythematosus Nuclear antigens
* Nephritis
* Skin lesions
* Arthritis
Rheumatoid Arthritis Antibody complexes: specifically IgM to IgG
* Arthritis
Post-streptococcal glomerulonephritis Streptococcal cell wall antigens
* Nephritis
Polyarteritis nodosa Hepatitis B virus surface antigen
* Systemic vasculitis
Reactive arthritis Several bacterial antigens
* Acute arthritis
Serum sickness Various
* Arthritis
* Vasculitis
* Nephritis
Arthus reaction Various
* Cutaneous vasculitis
Farmer's Lung Inhaled antigens (often mould or hay dust)
* Alveolar inflammation
Henoch–Schönlein purpura (IgA vasculitis) Unknown, likely respiratory pathogen
* Purpura
* Glomerulonephritis
Unless else specified in boxes, then ref is:[1]
Other examples are:
* Subacute bacterial endocarditis[2]
* Symptoms of malaria
## Signs and symptoms[edit]
Type III hypersensitivity occurs when there is an excess of antigen, leading to small immune complexes being formed that fix complement and are not cleared from the circulation. It involves soluble antigens that are not bound to cell surfaces (as opposed to those in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form.[3] Large complexes can be cleared by macrophages but macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as being highly pathogenic.[4]
Such depositions in tissues often induce an inflammatory response,[5] and can cause damage wherever they precipitate. The cause of damage is as a result of the action of cleaved complement anaphylotoxins C3a and C5a, which, respectively, mediate the induction of granule release from mast cells (from which histamine can cause urticaria), and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action, leading to tissue damage through frustrated phagocytosis by PMNs and macrophages).[6]
Immune Complex Glomerulonephritis, as seen in Henoch-Schönlein purpura; this is an example of IgA involvement in a nephropathy
The reaction can take hours, days, or even weeks to develop, depending on whether or not there is immunological memory of the precipitating antigen. Typically, clinical features emerge a week following initial antigen challenge, when the deposited immune complexes can precipitate an inflammatory response. Because of the nature of the antibody aggregation, tissues that are associated with blood filtration at considerable osmotic and hydrostatic gradient (e.g. sites of urinary and synovial fluid formation, kidney glomeruli and joint tissues respectively) bear the brunt of the damage. Hence, vasculitis, glomerulonephritis and arthritis are commonly associated conditions as a result of type III hypersensitivity responses.[7]
As observed under methods of histopathology, acute necrotizing vasculitis within the affected tissues is observed concomitant to neutrophilic infiltration, along with notable eosinophilic deposition (fibrinoid necrosis). Often, immunofluorescence microscopy can be used to visualize the immune complexes.[7] Skin response to a hypersensitivity of this type is referred to as an Arthus reaction, and is characterized by local erythema and some induration. Platelet aggregation, especially in microvasculature, can cause localized clot formation, leading to blotchy hemorrhages. This typifies the response to injection of foreign antigen sufficient to lead to the condition of serum sickness.[6]
## See also[edit]
* Type I hypersensitivity
* Type II hypersensitivity
* Type IV hypersensitivity
* Type V hypersensitivity
## References[edit]
1. ^ Table 5-3 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
2. ^ "Definition: immune complex disease from Online Medical Dictionary".[permanent dead link]
3. ^ "Hypersensitivity reactions". Retrieved 2008-09-26.
4. ^ Parham, Peter (2009). "12". The Immune System (3rd ed.). New York, NY: Garland Science. p. 390.
5. ^ "Chapter 19". Archived from the original on 2008-12-02. Retrieved 2009-01-08.
6. ^ a b Parham, Peter (2009). "12". The Immune System (3rd ed.). New York, NY: Garland Science. p. 389.
7. ^ a b Kumar, Vinay (2010). "6". Robbins and Cotran Pathologic Mechanisms of Disease (8th ed.). Philadelphia: Elsevier. pp. 204–205.
## External links[edit]
Classification
D
* MeSH: D007105
* v
* t
* e
Hypersensitivity and autoimmune diseases
Type I/allergy/atopy
(IgE)
Foreign
* Atopic eczema
* Allergic urticaria
* Allergic rhinitis (Hay fever)
* Allergic asthma
* Anaphylaxis
* Food allergy
* common allergies include: Milk
* Egg
* Peanut
* Tree nut
* Seafood
* Soy
* Wheat
* Penicillin allergy
Autoimmune
* Eosinophilic esophagitis
Type II/ADCC
* * IgM
* IgG
Foreign
* Hemolytic disease of the newborn
Autoimmune
Cytotoxic
* Autoimmune hemolytic anemia
* Immune thrombocytopenic purpura
* Bullous pemphigoid
* Pemphigus vulgaris
* Rheumatic fever
* Goodpasture syndrome
* Guillain–Barré syndrome
"Type V"/receptor
* Graves' disease
* Myasthenia gravis
* Pernicious anemia
Type III
(Immune complex)
Foreign
* Henoch–Schönlein purpura
* Hypersensitivity vasculitis
* Reactive arthritis
* Farmer's lung
* Post-streptococcal glomerulonephritis
* Serum sickness
* Arthus reaction
Autoimmune
* Systemic lupus erythematosus
* Subacute bacterial endocarditis
* Rheumatoid arthritis
Type IV/cell-mediated
(T cells)
Foreign
* Allergic contact dermatitis
* Mantoux test
Autoimmune
* Diabetes mellitus type 1
* Hashimoto's thyroiditis
* Multiple sclerosis
* Coeliac disease
* Giant-cell arteritis
* Postorgasmic illness syndrome
* Reactive arthritis
GVHD
* Transfusion-associated graft versus host disease
Unknown/
multiple
Foreign
* Hypersensitivity pneumonitis
* Allergic bronchopulmonary aspergillosis
* Transplant rejection
* Latex allergy (I+IV)
Autoimmune
* Sjögren syndrome
* Autoimmune hepatitis
* Autoimmune polyendocrine syndrome
* APS1
* APS2
* Autoimmune adrenalitis
* Systemic autoimmune disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Type III hypersensitivity | c0020951 | 2,323 | wikipedia | https://en.wikipedia.org/wiki/Type_III_hypersensitivity | 2021-01-18T18:33:58 | {"mesh": ["D007105"], "umls": ["C0020951"], "wikidata": ["Q5898315"]} |
Bloom syndrome is an inherited disorder characterized by short stature, a skin rash that develops after exposure to the sun, and a greatly increased risk of cancer.
People with Bloom syndrome are usually smaller than 97 percent of the population in both height and weight from birth, and they rarely exceed 5 feet tall in adulthood.
Affected individuals have skin that is sensitive to sun exposure, and they usually develop a butterfly-shaped patch of reddened skin across the nose and cheeks. A skin rash can also appear on other areas that are typically exposed to the sun, such as the back of the hands and the forearms. Small clusters of enlarged blood vessels (telangiectases) often appear in the rash; telangiectases can also occur in the eyes. Other skin features include patches of skin that are lighter or darker than the surrounding areas (hypopigmentation or hyperpigmentation respectively). These patches appear on areas of the skin that are not exposed to the sun, and their development is not related to the rashes.
People with Bloom syndrome have an increased risk of cancer. They can develop any type of cancer, but the cancers arise earlier in life than they do in the general population, and affected individuals often develop more than one type of cancer.
Individuals with Bloom syndrome have a high-pitched voice and distinctive facial features including a long, narrow face; a small lower jaw; and prominent nose and ears. Other features can include learning disabilities, an increased risk of diabetes, chronic obstructive pulmonary disease (COPD), and mild immune system abnormalities leading to recurrent infections of the upper respiratory tract, ears, and lungs during infancy. Men with Bloom syndrome usually do not produce sperm and as a result are unable to father children (infertile). Women with the disorder generally have reduced fertility and experience menopause at an earlier age than usual.
## Frequency
Bloom syndrome is a rare disorder. Only a few hundred affected individuals have been described in the medical literature, about one-third of whom are of Central and Eastern European (Ashkenazi) Jewish background.
## Causes
Mutations in the BLM gene cause Bloom syndrome. The BLM gene provides instructions for making a member of a protein family called RecQ helicases. Helicases are enzymes that attach (bind) to DNA and unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for several processes in the cell nucleus, including copying (replicating) DNA in preparation for cell division and repairing damaged DNA. Because RecQ helicases help maintain the structure and integrity of DNA, they are known as the "caretakers of the genome."
When a cell prepares to divide to form two cells, the DNA that makes up the chromosomes is copied so that each new cell will have two copies of each chromosome, one from each parent. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Sister chromatids occasionally exchange small sections of DNA during this time, a process known as sister chromatid exchange. Researchers suggest that these exchanges may be a response to DNA damage during the copying process. The BLM protein helps to prevent excess sister chromatid exchanges and is also involved in other processes that help maintain the stability of the DNA during the copying process.
BLM gene mutations result in the absence of functional BLM protein. As a result, the frequency of sister chromatid exchange is about 10 times higher than average. Exchange of DNA between chromosomes derived from the individual's mother and father are also increased in people with BLM gene mutations. In addition, chromosome breakage occurs more frequently in affected individuals. All of these changes are associated with gaps and breaks in the genetic material that impair normal cell activities and cause the health problems associated with this condition. Without the BLM protein, the cell is less able to repair DNA damage caused by ultraviolet light, which results in increased sun sensitivity. Genetic changes that allow cells to divide in an uncontrolled way lead to the cancers that occur in people with Bloom syndrome.
### Learn more about the gene associated with Bloom syndrome
* BLM
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Bloom syndrome | c0005859 | 2,324 | medlineplus | https://medlineplus.gov/genetics/condition/bloom-syndrome/ | 2021-01-27T08:25:18 | {"gard": ["915"], "mesh": ["D001816"], "omim": ["210900"], "synonyms": []} |
For a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see 605389.
Clinical Features
Naz et al. (2010) reported a 4-generation Pakistani family in which 4 individuals, 2 males and 2 females, had hypotrichosis. All 4 individuals had brown, thin, sparse hair on scalp, arms, and legs. Eyebrows and eyelashes were black and unaffected. At birth, hair on the scalp was sparse and thin. Following ritual shaving, the hair regrew sparsely in a few months. Teeth, nails, sweating, and hearing were normal, and there were no neurologic abnormalities or facial dysmorphisms. Heterozygous carrier individuals were indistinguishable from genotypically normal individuals.
Inheritance
The pedigree pattern in the family with hypotrichosis reported by Naz et al. (2010) was consistent with autosomal recessive inheritance.
Mapping
Using linkage analysis, Naz et al. (2010) mapped hereditary hypotrichosis in a 4-generation consanguineous Pakistani family to chromosome 10q11.23-q22.3, in a 28.5-Mb region between markers D10S538 (51.9 Mb) and D10S2327 (80.4 Mb) (build 36.2). A maximum multipoint lod score of 3.26 was obtained for several markers within the region.
Molecular Genetics
Naz et al. (2010) sequenced coding exons and splice junction sites of 4 genes in the critical region and failed to find any functional sequence variants. Linkage to genes known to be involved in hypotrichosis had been excluded.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Normal hearing Teeth \- Normal teeth SKIN, NAILS, & HAIR Skin \- Normal sweating Nails \- Normal nails Hair \- Sparse, thin scalp hair from birth \- Sparse, thin hair on arms \- Sparse, thin hair on legs \- Normal eyebrows \- Normal eyelashes MISCELLANEOUS \- Based on report of one consanguineous Pakistani family (last curated July 2017) ▲ 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
| HYPOTRICHOSIS 9 | c1854310 | 2,325 | omim | https://www.omim.org/entry/614237 | 2019-09-22T15:55:57 | {"doid": ["0110706"], "mesh": ["C537160"], "omim": ["614237"], "orphanet": ["55654"]} |
A severe form of oculocutaneous albinism type 1 (OCA1) characterized by complete absence of melanin and manifesting as white hair and skin, blue, fully translucent irises, nystagmus and misrouting of the optic nerves.
## Epidemiology
The worldwide prevalence of OCA1 is estimated at 1/40,000. OCA type 1A (OCA1A) is considered to account for about half of the overall OCA1 cases among non-Hispanic, Caucasian patients.
## Clinical description
Patients have white skin and hair at birth. Irises are blue to pink and fully translucent. These features do not change throughout a patient's life. Nystagmus may be present at birth or it may develop in the first 3 to 4 months of life. It continues throughout life but usually slows down after childhood and is less noticeable when a person is relaxed and well rested. Visual acuity ranges from 20/100 and 20/400 and an alternating strabismus is often present. The reduction in visual acuity is associated with foveal hypoplasia. Severe photophobia is common. Nevi and ephelides are common but are unpigmented and pink. Patients do not tan, and if proper sun protection methods are not followed, skin becomes rough, coarse, thickened and can have solar keratoses. Patients have an increased risk of developing basal and squamous cell carcinomas but melanomas are rare.
## Etiology
OCA1A is caused by a mutation in the TYR gene (11q14.2) encoding tyrosinase. The mutation leads to a completely inactive or incomplete tyrosinase enzyme polypeptide. Melanocytes contain no melanin, as without this enzyme the melanin biosynthetic pathway is blocked.
## Diagnostic methods
The characteristic clinical findings along with confirmatory genetic testing are used to diagnose OCA1A. Ophthalmologic examination reveals visualization of the choroidal blood vessels, reduced retinal pigment and foveal hypoplasia. Alternating strabismus, reduced stereoscopic vision, and an altered visual evoked potential (VEP) are associated with the characteristic misrouting of the optic nerves at the chiasm. Molecular genetic testing is usually necessary to make the correct diagnosis of this subtype.
## Differential diagnosis
Differential diagnoses include the other forms of OCA and X-linked ocular albinism (XLOA) as well as syndromes with albinism as a feature such as Hermansky-Pudlak syndromes 1-11, Chediak-Higashi syndrome, Griscelli syndromes 1-3, and Waardenburg syndrome type II.
## Antenatal diagnosis
Prenatal testing is possible for at risk pregnancies by molecular genetic testing.
## Genetic counseling
This disorder is inherited autosomal recessively. 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
Annual ophthalmologic examination is necessary and corrective lenses or glasses are given to improve visual acuity. Dark glasses may be needed to relieve photophobia. Strabismus surgery can be performed for functional or cosmetic reasons. Protection from sunlight is imperative and patients should wear clothing and sunscreen on exposed skin to prevent burning and reduce the risk of skin cancer. Annual skin examinations should also be performed to identify any pre-cancerous or cancerous lesions.
## Prognosis
OCA1A is not life threatening, unless malignancies develop, and remains stable after childhood. The medical and social consequences can however have major impacts on a patient's daily 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
| Oculocutaneous albinism type 1A | c0268494 | 2,326 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79431 | 2021-01-23T18:28:01 | {"mesh": ["C537728"], "omim": ["203100"], "icd-10": ["E70.3"], "synonyms": ["OCA1A", "Tyrosinase-negative oculocutaneous albinism"]} |
Abortion in Andorra is banned except in cases where it is necessary to save the life of a pregnant woman.[1][2]
In Andorra, a woman who performs an abortion on herself or gives consent to another person to perform an abortion is subject to up two and a half years imprisonment. A person who performs an abortion with the consent of a pregnant woman is subject to imprisonment up to four years; if she or he is a medical practitioner and aborted the child for financial profit, the maximum penalty is six years in prison. If termination of pregnancy is performed without consent of the pregnant woman, the maximum penalty is ten years in prison. If a pregnant woman dies due to an abortion, the maximum penalty is 12 years in prison.[1][2]
Though the law has no explicit exceptions to the prohibition,[1][3] general criminal law principles of necessity provide a legal basis for abortions to be performed when necessary to save the life of the mother.[1]
Women in Andorra who choose to terminate a pregnancy usually go to either neighboring Spain or France.[4]
As of 2018[update], a movement to legalize abortion in Andorra has prompted Pope Francis to intervene. Because the Bishop of Urgell, Joan Enric Vives Sicília, is a co-prince of the principality, his approval of legalization would, according to the Pope, result in the co-prince's abdication and withdrawal of support from the Holy See. This situation could have an impact on the nature of Andorra's governance and its independence from Spain and France.[5]
## References[edit]
1. ^ a b c d Abortion Policies: A Global Review (DOC). 2. United Nations Population Division. 2002. Retrieved 25 March 2014.
2. ^ a b "Penal Code of 11 July 1990. (Butlletí Oficial del Principat d'Andorra, Vol. 2, No. 21, 21 July 1990, pp. 378-96.)". 1990. Retrieved 25 March 2014.
3. ^ "Facts and figures about abortion in the European Region". World Health Organization, Europe. World Health Organization. Archived from the original on 14 August 2014. Retrieved 13 August 2014.
4. ^ White, Christna (9 April 2018). "The Ms. Q&A: Vanessa Mendoza Cortés is Demanding a Better Future for Women in Andorra". Ms.blog.
5. ^ https://www.diariandorra.ad/noticies/nacional/2018/11/05/el_vatica_avisa_que_avortament_faria_abdicar_coprincep_137655_1125.html
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
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*[nM]: nanomolars
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| Abortion in Andorra | None | 2,327 | wikipedia | https://en.wikipedia.org/wiki/Abortion_in_Andorra | 2021-01-18T18:37:52 | {"wikidata": ["Q4668439"]} |
Not to be confused with Biceps femoris tendon rupture.
Distal biceps tendon rupture, with proximal retraction of the muscle.
Panoramic ultrasonography of a proximal biceps tendon rupture. Top image shows the contralateral normal side, and lower image shows a retracted muscle, with a hematoma filling out the proximal space.
A biceps tendon rupture is a complete or partial rupture of a tendon of the biceps brachii muscle. It can affect the distal tendon, or either/both of the proximal tendons, attached to the long and short head of the muscle, respectively.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Treatment
* 4 References
## Signs and symptoms[edit]
When a biceps tendon ruptures, the muscle belly changes position in the arm.[1] The bulge that forms is often known as Popeye's sign, due to the similarity in appearance to the cartoon character Popeye.[1]
## Causes[edit]
A biceps tendon rupture may occur during athletic activities, however avulsion injuries of the distal biceps tendon are frequently occupational in nature and sustained during forceful, eccentric contraction of the biceps muscle while lifting.[2]
## Treatment[edit]
Acute rupture of the distal biceps tendon can be treated nonoperatively with acceptable results,[3] but because the injury can lead to 30% loss of elbow flexion strength and 30-50% loss of forearm supination strength, surgical repair is generally recommended.[4][5][6] Complete distal biceps tears are commonly treated with re-attachment of the biceps tendon to its native insertion on the tuberosity of the radius using bone tunnels, suture buttons, or suture anchors.[7][4][8] Proximal ruptures of the long head of the biceps tendon can be surgically addressed by two different techniques. Biceps tenodesis includes release of the long head of the biceps tendon off of its insertion on the glenoid and re-attachment by screw or suture anchor fixation to the humerus. Biceps tenotomy consists of simple release of the long head of the biceps without reattachment to the humerus, allowing the tendon to retract into the soft tissues of the proximal upper arm.[2] Degeneration of the tendon can cause partial tears and are rarely associated with a traumatic event.[citation needed]
Treatment of a biceps tear depends on the severity of the injury. In most cases, the muscle will heal over time with no corrective surgery. Applying cold pressure and using anti-inflammatory medications will ease pain and reduce swelling. More severe injuries require surgery and post-op physical therapy to regain strength and functionality in the muscle. Corrective surgeries of this nature are typically reserved for elite athletes who rely on a complete recovery.[9]
Wikimedia Commons has media related to Biceps tendon rupture.
## References[edit]
1. ^ a b Yoshida, Naoki; Tsuchida, Yoshihiko (2017-11-16). ""Popeye" Sign". New England Journal of Medicine. 377 (20): 1976–1976. doi:10.1056/NEJMicm1704705. ISSN 0028-4793. PMID 29141167.
2. ^ a b Miller MD, Thompson SR, DeLee J, Drez D (2015). DeLee & Drez's orthopaedic sports medicine : principles and practice (Fourth ed.). Philadelphia, PA. ISBN 978-1-4557-4376-6. OCLC 880421005.
3. ^ Freeman CR, McCormick KR, Mahoney D, Baratz M, Lubahn JD (October 2009). "Nonoperative treatment of distal biceps tendon ruptures compared with a historical control group". The Journal of Bone and Joint Surgery. American Volume. 91 (10): 2329–34. doi:10.2106/jbjs.h.01150. PMID 19797566.
4. ^ a b Morrey BF, Askew LJ, An KN, Dobyns JH (March 1985). "Rupture of the distal tendon of the biceps brachii. A biomechanical study". The Journal of Bone and Joint Surgery. American Volume. 67 (3): 418–21. doi:10.2106/00004623-198567030-00011. PMID 3972866.
5. ^ Baker BE, Bierwagen D (March 1985). "Rupture of the distal tendon of the biceps brachii. Operative versus non-operative treatment". The Journal of Bone and Joint Surgery. American Volume. 67 (3): 414–7. doi:10.2106/00004623-198567030-00010. PMID 3972865.
6. ^ Nesterenko S, Domire ZJ, Morrey BF, Sanchez-Sotelo J (March 2010). "Elbow strength and endurance in patients with a ruptured distal biceps tendon". Journal of Shoulder and Elbow Surgery. 19 (2): 184–9. doi:10.1016/j.jse.2009.06.001. PMID 19664936.
7. ^ Sotereanos DG, Pierce TD, Varitimidis SE (May 2000). "A simplified method for repair of distal biceps tendon ruptures". Journal of Shoulder and Elbow Surgery. 9 (3): 227–33. doi:10.1067/mse.2000.105136. PMID 10888168.
8. ^ Bain GI, Prem H, Heptinstall RJ, Verhellen R, Paix D (March 2000). "Repair of distal biceps tendon rupture: a new technique using the Endobutton". Journal of Shoulder and Elbow Surgery. 9 (2): 120–6. doi:10.1067/2000.102581. PMID 10810691.
9. ^ "Bicep tear - Muscular Injuries". Sports Medicine Information.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Biceps tendon rupture | c0347952 | 2,328 | wikipedia | https://en.wikipedia.org/wiki/Biceps_tendon_rupture | 2021-01-18T18:53:51 | {"wikidata": ["Q879257"]} |
Not to be confused with Dupuytren fracture.
Disease with gradual bending of the fingers due to scar tissue build-up within the palms
Dupuytren's contracture
Other namesDupuytren's disease, Morbus Dupuytren, Viking disease, and Celtic hand,[1] contraction of palmar fascia, palmar fascial fibromatosis, palmar fibromas[2]
Dupuytren's contracture of the ring finger
Pronunciation
* /dəˌpwiːˈtræ̃z, -ˈpwiːtrənz/[3]
SpecialtyRheumatology
SymptomsOne or more fingers permanently bent in a flexed position, hard nodule just under the skin of the palm[2]
ComplicationsTrouble preparing food or writing[2]
Usual onsetGradual onset in males over 50[2]
CausesUnknown[4]
Risk factorsFamily history, alcoholism, smoking, thyroid problems, liver disease, diabetes, epilepsy[2][4]
Diagnostic methodBased on symptoms[4]
TreatmentSteroid injections, clostridial collagenase injections, surgery[4][5]
Frequency~5% (US)[2]
Dupuytren's contracture (also called Dupuytren's disease, Morbus Dupuytren, Viking disease, and Celtic hand) is a condition in which one or more fingers become permanently bent in a flexed position.[2] It is named after Guillaume Dupuytren, who first described the underlying mechanism of action followed by the first successful operation in 1831 and publication of the results in The Lancet in 1834.[6] It usually begins as small, hard nodules just under the skin of the palm,[2] then worsens over time until the fingers can no longer be straightened. While typically not painful, some aching or itching may be present.[2] The ring finger followed by the little and middle fingers are most commonly affected.[2] The condition can interfere with activities such as preparing food and writing.[2]
The cause is unknown.[4] Risk factors include family history, alcoholism, smoking, thyroid problems, liver disease, diabetes, previous hand trauma, and epilepsy.[2][4] The underlying mechanism involves the formation of abnormal connective tissue within the palmar fascia.[2] Diagnosis is usually based on symptoms.[4]
Initial treatment is typically with steroid injections into the affected area, occupational therapy, and physical therapy.[4] Among those who worsen, clostridial collagenase injections or surgery may be tried.[4][5] While radiation therapy is used to treat this condition, the evidence for this use is poor.[7] The condition may recur despite treatment.[4]
Dupuytren's most often occurs in males over the age of 50.[2] It mostly affects white people, and is rare among Asians and Africans.[6] It is sometimes called the "Viking disease", since it is more common among those of Nordic descent.[6] In the United States about 5% of people are affected at some point in time, while in Norway about 30% of men over 60 years old have the condition.[2] In the United Kingdom, about 20% of people over 65 have some form of the disease.[6]
## Contents
* 1 Signs and symptoms
* 1.1 Related conditions
* 2 Risk factors
* 2.1 Non-modifiable
* 2.2 Modifiable
* 2.3 Other conditions
* 3 Diagnosis
* 3.1 Types
* 4 Treatment
* 4.1 Surgery
* 4.1.1 Limited fasciectomy
* 4.1.2 Wide-awake fasciectomy
* 4.1.3 Dermofasciectomy
* 4.1.4 Segmental fasciectomy with/without cellulose
* 4.2 Less invasive treatments
* 4.2.1 Percutaneous needle fasciotomy
* 4.2.2 Extensive percutaneous aponeurotomy and lipografting
* 4.2.3 Collagenase
* 4.3 Radiation therapy
* 4.4 Alternative medicine
* 4.5 Postoperative care
* 5 Prognosis
* 6 Notable cases
* 7 References
* 8 External links
## Signs and symptoms[edit]
Dupuytren's contracture of the right little finger. Arrow marks the area of scarring
Typically, Dupuytren's contracture first presents as a thickening or nodule in the palm, which initially can be with or without pain.[8] Later in the disease process, which can be years later,[9] there is painless increasing loss of range of motion of the affected finger(s). The earliest sign of a contracture is a triangular "puckering" of the skin of the palm as it passes over the flexor tendon just before the flexor crease of the finger, at the metacarpophalangeal (MCP) joint.
Generally, the cords or contractures are painless, but, rarely, tenosynovitis can occur and produce pain. The most common finger to be affected is the ring finger; the thumb and index finger are much less often affected.[10] The disease begins in the palm and moves towards the fingers, with the metacarpophalangeal (MCP) joints affected before the proximal interphalangeal (PIP) joints.[11]
In Dupuytren's contracture, the palmar fascia within the hand becomes abnormally thick, which can cause the fingers to curl and can impair finger function. The main function of the palmar fascia is to increase grip strength; thus, over time, Dupuytren's contracture decreases a person's ability to hold objects. People may report pain, aching, and itching with the contractions. Normally, the palmar fascia consists of collagen type I, but in Dupuytren sufferers, the collagen changes to collagen type III, which is significantly thicker than collagen type I.[citation needed]
### Related conditions[edit]
People with severe involvement often show lumps on the back of their finger joints (called "Garrod's pads", "knuckle pads", or "dorsal Dupuytren nodules"), and lumps in the arch of the feet (plantar fibromatosis or Ledderhose disease).[12] In severe cases, the area where the palm meets the wrist may develop lumps.
## Risk factors[edit]
Dupuytren's contracture is a non-specific affliction, but primarily affects:
### Non-modifiable[edit]
* People of Scandinavian or Northern European ancestry;[13] it has been called the "Viking disease",[6] though it is also widespread in some Mediterranean countries, e.g., Spain[14] and Bosnia.[15][16] Dupuytren's is unusual among ethnic groups such as Chinese and Africans.[17]
* Men rather than women; men are more likely to develop the condition (80%)[10][13][18]
* People over the age of 50 (5% to 15% of men in that group in the US); the likelihood of getting Dupuytren's disease increases with age[10][17][18]
* People with a family history (60% to 70% of those afflicted have a genetic predisposition to Dupuytren's contracture)[10][19]
### Modifiable[edit]
* Smokers, especially those who smoke 25 cigarettes or more a day[17][20]
* Thinner people, i.e., those with a lower-than-average body mass index.[17]
* Manual workers[17]
* Alcoholics[6][20]
### Other conditions[edit]
* People with a higher-than-average fasting blood glucose level[17]
* People with previous hand injury[10]
* People with Ledderhose disease (plantar fibromatosis)[10]
* People with epilepsy (possibly due to anti-convulsive medication)[21]
* People with diabetes mellitus[6][21]
* People with HIV[6]
* Previous myocardial infarction[17][18]
In one study, those with stage 2 of the disease were found to have a slightly increased risk of mortality, especially from cancer.[22]
## Diagnosis[edit]
### Types[edit]
According to the American Dupuytren's specialist Dr. Charles Eaton, there may be three types of Dupuytren's disease:[23]
* Type 1: A very aggressive form of the disease found in only 3% of people with Dupuytren's, which can affect men under 50 with a family history of Dupuytren's. It is often associated with other symptoms such as knuckle pads and Ledderhose disease. This type is sometimes known as Dupuytren's diathesis.[24]
* Type 2: The more normal type of Dupuytren's disease, usually found in the palm only, and which generally begins above the age of 50. According to Eaton, this type may be made more severe by other factors such as diabetes or heavy manual labor.[23]
* Type 3: A mild form of Dupuytren's which is common among diabetics or which may also be caused by certain medications, such as the anti-convulsants taken by people with epilepsy. This type does not lead to full contracture of the fingers, and is probably not inherited.[23]
## Treatment[edit]
Treatment is indicated when the so-called table-top test is positive. With this test, the person places their hand on a table. If the hand lies completely flat on the table, the test is considered negative. If the hand cannot be placed completely flat on the table, leaving a space between the table and a part of the hand as big as the diameter of a ballpoint pen, the test is considered positive and surgery or other treatment may be indicated. Additionally, finger joints may become fixed and rigid.There are several types of treatment, with some hands needing repeated treatment.
The main categories listed by the International Dupuytren Society in order of stage of disease are radiation therapy, needle aponeurotomy (NA), collagenase injection, and hand surgery. As of 2016[update] the evidence on the efficacy of radiation therapy was considered inadequate in quantity and quality, and difficult to interpret because of uncertainty about the natural history of Dupuytren's disease.[25]
Needle aponeurotomy is most effective for Stages I and II, covering 6–90 degrees of deformation of the finger. However, it is also used at other stages.
Collagenase injection is likewise most effective for Stages I and II. However, it is also used at other stages.
Hand surgery is effective at stage I to stage IV.[26]
### Surgery[edit]
On 12 June 1831, Dupuytren performed a surgical procedure on a person with contracture of the 4th and 5th digits who had been previously told by other surgeons that the only remedy was cutting the flexor tendons. He described the condition and the operation in The Lancet in 1834[27] after presenting it in 1833, and posthumously in 1836 in a French publication by Hôtel-Dieu de Paris.[28] The procedure he described was a minimally invasive needle procedure.
Because of high recurrence rates,[citation needed] new surgical techniques were introduced, such as fasciectomy and then dermofasciectomy. Most of the diseased tissue is removed with these procedures.Recurrence rates are high.[clarify] For some individuals, the partial insertion of "K-wires" into either the DIP or PIP joint of the affected digit for a period of a least 21 days to fuse the joint is the only way to halt the disease's progress. After removal of the wires, the joint is fixed into flexion, which is considered preferable to fusion at extension.
In extreme cases, amputation of fingers may be needed for severe or recurrent cases or after surgical complications.[29]
#### Limited fasciectomy[edit]
Hand immediately after surgery, and completely healed
Limited/selective fasciectomy removes the pathological tissue, and is a common approach.[30][31] Low-quality evidence suggests that fasciectomy may be more effective for people with advanced Dupuytren's contractures.[32]
During the procedure, the person is under regional or general anesthesia. A surgical tourniquet prevents blood flow to the limb.[33] The skin is often opened with a zig-zag incision but straight incisions with or without Z-plasty are also described and may reduce damage to neurovascular bundles.[34] All diseased cords and fascia are excised.[30][31][33] The excision has to be very precise to spare the neurovascular bundles.[33] Because not all the diseased tissue is visible macroscopically, complete excision is uncertain.[31]
A 20-year review of surgical complications associated with fasciectomy showed that major complications occurred in 15.7% of cases, including digital nerve injury (3.4%), digital artery injury (2%), infection (2.4%), hematoma (2.1%), and complex regional pain syndrome (5.5%), in addition to minor complications including painful flare reactions in 9.9% of cases and wound healing complications in 22.9% of cases.[35] After the tissue is removed the incision is closed. In the case of a shortage of skin, the transverse part of the zig-zag incision is left open. Stitches are removed 10 days after surgery.[33]
After surgery, the hand is wrapped in a light compressive bandage for one week. Flexion and extension of the fingers can start as soon as the anaesthesia has resolved. It is common to experience tingling within the first week after surgery.[32] Hand therapy is often recommended.[33] Approximately 6 weeks after surgery the patient is able completely to use the hand.[36]
The average recurrence rate is 39% after a fasciectomy after a median interval of about 4 years.[37]
#### Wide-awake fasciectomy[edit]
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Limited/selective fasciectomy under local anesthesia (LA) with epinephrine but no tourniquet is possible. In 2005, Denkler described the technique.[38][39]
#### Dermofasciectomy[edit]
Dermofasciectomy is a surgical procedure that may be used when:
* The skin is clinically involved (pits, tethering, deficiency, etc)
* The risk of recurrence is high and the skin appears uninvolved (subclinical skin involvement occurs in ~50% of cases[40])
* Recurrent disease.[31] Similar to a limited fasciectomy, the dermofasciectomy removes diseased cords, fascia, and the overlying skin.[41]
Typically, the excised skin is replaced with a skin graft, usually full thickness,[31] consisting of the epidermis and the entire dermis. In most cases the graft is taken from the antecubital fossa (the crease of skin at the elbow joint) or the inner side of the upper arm.[41][42] This place is chosen because the skin color best matches the palm's skin color. The skin on the inner side of the upper arm is thin and has enough skin to supply a full-thickness graft. The donor site can be closed with a direct suture.[41]
The graft is sutured to the skin surrounding the wound. For one week the hand is protected with a dressing. The hand and arm are elevated with a sling. The dressing is then removed and careful mobilization can be started, gradually increasing in intensity.[41] After this procedure the risk of recurrence is minimised,[31][41][42] but Dupuytren's can recur in the skin graft[43] and complications from surgery may occur.[vague][44]
#### Segmental fasciectomy with/without cellulose[edit]
Segmental fasciectomy involves excising part(s) of the contracted cord so that it disappears or no longer contracts the finger. It is less invasive than the limited fasciectomy, because not all the diseased tissue is excised and the skin incisions are smaller.[45]
The person is placed under regional anesthesia and a surgical tourniquet is used. The skin is opened with small curved incisions over the diseased tissue. If necessary, incisions are made in the fingers.[45] Pieces of cord and fascia of approximately one centimeter are excised. The cords are placed under maximum tension while they are cut. A scalpel is used to separate the tissues.[45] The surgeon keeps removing small parts until the finger can fully extend.[45][46] The person is encouraged to start moving his or her hand the day after surgery. They wear an extension splint for two to three weeks, except during physical therapy.[45]
The same procedure is used in the segmental fasciectomy with cellulose implant. After the excision and a careful hemostasis, the cellulose implant is placed in a single layer in between the remaining parts of the cord.[46]
After surgery people wear a light pressure dressing for four days, followed by an extension splint. The splint is worn continuously during nighttime for eight weeks. During the first weeks after surgery the splint may be worn during daytime.[46]
### Less invasive treatments[edit]
Studies have been conducted for percutaneous release, extensive percutaneous aponeurotomy with lipografting and collagenase. These treatments show promise.[47][48][49][50]
#### Percutaneous needle fasciotomy[edit]
Needle aponeurotomy is a minimally-invasive technique where the cords are weakened through the insertion and manipulation of a small needle. The cord is sectioned at as many levels as possible in the palm and fingers, depending on the location and extent of the disease, using a 25-gauge needle mounted on a 10 ml syringe.[47] Once weakened, the offending cords can be snapped by putting tension on the finger(s) and pulling the finger(s) straight. After the treatment a small dressing is applied for 24 hours, after which people are able to use their hands normally. No splints or physiotherapy are given.[47]
The advantage of needle aponeurotomy is the minimal intervention without incision (done in the office under local anesthesia) and the very rapid return to normal activities without need for rehabilitation, but the nodules may resume growing.[51] A study reported postoperative gain is greater at the MCP-joint level than at the level of the IP-joint and found a reoperation rate of 24%; complications are scarce.[52] Needle aponeurotomy may be performed on fingers that are severely bent (stage IV), and not just in early stages. A 2003 study showed 85% recurrence rate after 5 years.[53]
A comprehensive review of the results of needle aponeurotomy in 1,013 fingers was performed by Gary M. Pess, MD, Rebecca Pess, DPT, and Rachel Pess, PsyD, and published in the Journal of Hand Surgery April 2012. Minimal follow-up was 3 years. Metacarpophalangeal joint (MP) contractures were corrected at an average of 99% and proximal interphalangeal joint (PIP) contractures at an average of 89% immediately post procedure. At final follow-up, 72% of the correction was maintained for MP joints and 31% for PIP joints. The difference between the final corrections for MP versus PIP joints was statistically significant. When a comparison was performed between people aged 55 years and older versus under 55 years, there was a statistically significant difference at both MP and PIP joints, with greater correction maintained in the older group.
Gender differences were not statistically significant. Needle aponeurotomy provided successful correction to 5° or less contracture immediately post procedure in 98% (791) of MP joints and 67% (350) of PIP joints. There was recurrence of 20° or less over the original post-procedure corrected level in 80% (646) of MP joints and 35% (183) of PIP joints. Complications were rare except for skin tears, which occurred in 3.4% (34) of digits. This study showed that NA is a safe procedure that can be performed in an outpatient setting. The complication rate was low, but recurrences were frequent in younger people and for PIP contractures.[54]
#### Extensive percutaneous aponeurotomy and lipografting[edit]
A technique introduced in 2011 is extensive percutaneous aponeurotomy with lipografting.[48] This procedure also uses a needle to cut the cords. The difference with the percutaneous needle fasciotomy is that the cord is cut at many places. The cord is also separated from the skin to make place for the lipograft that is taken from the abdomen or ipsilateral flank.[48] This technique shortens the recovery time. The fat graft results in supple skin.[48]
Before the aponeurotomy, a liposuction is done to the abdomen and ipsilateral flank to collect the lipograft.[48] The treatment can be performed under regional or general anesthesia. The digits are placed under maximal extension tension using a firm lead hand retractor. The surgeon makes multiple palmar puncture wounds with small nicks. The tension on the cords is crucial, because tight constricting bands are most susceptible to be cut and torn by the small nicks, whereas the relatively loose neurovascular structures are spared. After the cord is completely cut and separated from the skin the lipograft is injected under the skin. A total of about 5 to 10 ml is injected per ray.[48]
After the treatment the person wears an extension splint for 5 to 7 days. Thereafter the person returns to normal activities and is advised to use a night splint for up to 20 weeks.[48]
#### Collagenase[edit]
Main article: Collagenase clostridium histolyticum
Collagenase enzyme injection: before, next day, and two weeks after first treatment
Clostridial collagenase injections have been found to be more effective than placebo.[5] The cords are weakened through the injection of small amounts of the enzyme collagenase, which breaks peptide bonds in collagen.[49][55][56][57][50][excessive citations]
The treatment with collagenase is different for the MCP joint and the PIP joint. In a MCP joint contracture the needle must be placed at the point of maximum bowstringing of the palpable cord.[49]
The needle is placed vertically on the bowstring. The collagenase is distributed across three injection points.[49] For the PIP joint the needle must be placed not more than 4 mm distal to palmar digital crease at 2–3 mm depth.[49] The injection for PIP consists of one injection filled with 0.58 mg CCH 0.20 ml.[50] The needle must be placed horizontal to the cord and also uses a 3-point distribution.[49] After the injection the person's hand is wrapped in bulky gauze dressing and must be elevated for the rest of the day. After 24 hours the person returns for passive digital extension to rupture the cord. Moderate pressure for 10–20 seconds ruptures the cord.[49]
After the treatment with collagenase the person should use a night splint and perform digital flexion/extension exercises several times per day for 4 months.[49]
In February 2010 the US Food and Drug Administration (FDA) approved injectable collagenase extracted from Clostridium histolyticum for the treatment of Dupuytren's contracture in adults with a palpable Dupuytren's cord. (Three years later, it was approved as well for the treatment of the sometimes related Peyronie's disease.)[58][9] In 2011 its use for the treatment of Dupuytren's contracture was approved as well by the European Medicines Agency, and it received similar approval in Australia in 2013.[9]
### Radiation therapy[edit]
Shows the beam's-eye view of the radiotherapy portal on the hand's surface, with the lead shield cut-out placed in the machine's gantry
Radiation therapy has been used mostly for early-stage disease, but is unproven.[7] Evidence to support its use as of 2017[update], however, was poor—efforts to gather evidence are complicated due to a poor understanding of how the condition develops over time.[7][25] It has only been looked at in early disease.[7]
### Alternative medicine[edit]
Several alternate therapies such as vitamin E treatment have been studied, though without control groups. Most doctors do not value those treatments.[59] None of these treatments stops or cures the condition permanently. A 1949 study of vitamin E therapy found that "In twelve of the thirteen patients there was no evidence whatever of any alteration. ... The treatment has been abandoned."[60][61]
Laser treatment (using red and infrared at low power) was informally discussed in 2013 at an International Dupuytren Society forum,[62] as of which time little or no formal evaluation of the techniques had been completed.
### Postoperative care[edit]
Postoperative care involves hand therapy and splinting. Hand therapy is prescribed to optimize post-surgical function and to prevent joint stiffness.[citation needed]
Besides hand therapy, many surgeons advise the use of static or dynamic splints after surgery to maintain finger mobility. The splint is used to provide prolonged stretch to the healing tissues and prevent flexion contractures. Although splinting is a widely used post-operative intervention, evidence of its effectiveness is limited,[63] leading to variation in splinting approaches. Most surgeons use clinical experience to decide whether to splint.[64] Cited advantages include maintenance of finger extension and prevention of new flexion contractures. Cited disadvantages include joint stiffness, prolonged pain, discomfort,[64] subsequently reduced function and edema.
A third approach emphasizes early self-exercise and stretching.[39]
## Prognosis[edit]
Dupuytren's disease has a high recurrence rate, especially when a person has so-called Dupuytren's diathesis. The term diathesis relates to certain features of Dupuytren's disease, and indicates an aggressive course of disease.[24]
The presence of all new Dupuytren's diathesis factors increases the risk of recurrent Dupuytren's disease by 71%, compared with a baseline risk of 23% in people lacking the factors.[24] In another study the prognostic value of diathesis was evaluated. It was concluded that presence of diathesis can predict recurrence and extension.[65] A scoring system was made to evaluate the risk of recurrence and extension, based on the following values: bilateral hand involvement, little-finger surgery, early onset of disease, plantar fibrosis, knuckle pads, and radial side involvement.[65]
Minimally invasive therapies may precede higher recurrence rates. Recurrence lacks a consensus definition. Furthermore, different standards and measurements follow from the various definitions.[citation needed]
## Notable cases[edit]
* Misha Dichter (born 1945), American pianist[66]
* John Elway (born 1960), American football player[67]
* Bill Frindall (1939–2009), English cricket player and statistician, who had a finger amputated.[68]
* Tim Herron (born 1970), American golfer[69]
* Prince Joachim of Denmark (born 1969)[70]
* Paul Newman (1925–2008), American actor and film director[71]
* Bill Nighy (born 1949), English actor[72]
* Ronald Reagan (1911–2004), American President and actor[73]
* Frank Sinatra (1915–1998), American singer, actor, and producer[74]
* Margaret Thatcher (1925–2013), Prime Minister of the United Kingdom[73]
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51. ^ Lellouche, Henri (2008). "Maladie de Dupuytren : La chirurgie n'est plus obligatoire" [Dupuytren's contracture: surgery is no longer necessary]. La Presse Médicale (in French). 37 (12): 1779–81. doi:10.1016/j.lpm.2008.07.012. PMID 18922672.
52. ^ Foucher, G (2003). "Percutaneous needle aponeurotomy: Complications and results". The Journal of Hand Surgery: Journal of the British Society for Surgery of the Hand. 28 (5): 427–31. doi:10.1016/S0266-7681(03)00013-5. PMID 12954251. S2CID 11181513.
53. ^ Van Rijssen, Annet L.; Ter Linden, Hein; Werker, Paul M. N. (2012). "Five-Year Results of a Randomized Clinical Trial on Treatment in Dupuytrenʼs Disease". Plastic and Reconstructive Surgery. 129 (2): 469–77. doi:10.1097/PRS.0b013e31823aea95. PMID 21987045. S2CID 24454361.
54. ^ Pess, Gary M.; Pess, Rebecca M.; Pess, Rachel A. (2012). "Results of Needle Aponeurotomy for Dupuytren Contracture in over 1,000 Fingers". The Journal of Hand Surgery. 37 (4): 651–6. doi:10.1016/j.jhsa.2012.01.029. PMID 22464232.
55. ^ Badalamente, Marie A.; Hurst, Lawrence C. (2007). "Efficacy and Safety of Injectable Mixed Collagenase Subtypes in the Treatment of Dupuytren's Contracture". The Journal of Hand Surgery. 32 (6): 767–74. doi:10.1016/j.jhsa.2007.04.002. PMID 17606053.
56. ^ Badalamente, Marie A.; Hurst, Lawrence C. (2000). "Enzyme injection as nonsurgical treatment of Dupuytren's disease". The Journal of Hand Surgery. 25 (4): 629–36. doi:10.1053/jhsu.2000.6918. PMID 10913202. S2CID 24029657.
57. ^ Badalamente, Marie A.; Hurst, Lawrence C.; Hentz, Vincent R. (2002). "Collagen as a clinical target: Nonoperative treatment of Dupuytren's disease". The Journal of Hand Surgery. 27 (5): 788–98. doi:10.1053/jhsu.2002.35299. PMID 12239666.
58. ^ "FDA Approves Xiaflex for Debilitating Hand Condition". Fda.gov. 2010-02-02. Archived from the original on 2012-11-26. Retrieved 2013-02-27.
59. ^ Proposed Natural Treatments for Dupuytren's Contracture, EBSCO Complementary and Alternative Medicine Review Board, 2 February 2011 Archived 23 July 2011 at the Wayback Machine. Date February 2011.
60. ^ King, Raymond A (August 1949). "Vitamin E therapy in Dupuytren's contracture - Examination of the Claim that Vitamin Therapy is Successful" (PDF). The Bone & Joint Journal. 31B (3): 443.
61. ^ Therapies for Dupuytren's contracture and Ledderhose disease with possibly less benefit, International Dupuytren Society, 19 January 2011 Archived 14 March 2011 at the Wayback Machine.
62. ^ Cold Laser Treatment Archived 2013-11-09 at the Wayback Machine at International Dupuytren Society online forum. Accessed: 28 August 2012.
63. ^ Jerosch-Herold, Christina; Shepstone, Lee; Chojnowski, Adrian J.; Larson, Debbie (2008). "Splinting after contracture release for Dupuytren's contracture (SCoRD): Protocol of a pragmatic, multi-centre, randomized controlled trial". BMC Musculoskeletal Disorders. 9: 62. doi:10.1186/1471-2474-9-62. PMC 2386788. PMID 18447898.
64. ^ a b Larson, Debbie; Jerosch-Herold, Christina (2008). "Clinical effectiveness of post-operative splinting after surgical release of Dupuytren's contracture: A systematic review". BMC Musculoskeletal Disorders. 9: 104. doi:10.1186/1471-2474-9-104. PMC 2518149. PMID 18644117.
65. ^ a b Abe, Y. (2004). "An objective method to evaluate the risk of recurrence and extension of Dupuytren's disease". The Journal of Hand Surgery: Journal of the British Society for Surgery of the Hand. 29 (5): 427–30. doi:10.1016/j.jhsb.2004.06.004. PMID 15336743. S2CID 27542382.
66. ^ Pollack, Andrew (March 15, 2010). "Triumph for Drug to Straighten Clenched Fingers". The New York Times. Archived from the original on March 18, 2010.
67. ^ Chelsea Howard (August 22, 2019). "Broncos' John Elway opens up about 15-year battle with debilitating hand condition". Sporting News.
68. ^ Jonathan Agnew, Aggers' Ashes (London, 2011), page 103
69. ^ Helen Ross (November 6, 2018). "Herron dealing with early stages of Dupuytren's contracture". PGATour.
70. ^ "Joachim opereret for krumme fingre". HER&NU. March 17, 2013. Archived from the original on October 29, 2013.
71. ^ "Local MD Will Speak on Crippling Hand Disease Which Affects Many Seniors," Sun-Sentinel, July 15, 2014
72. ^ Farndale, Nigel (February 8, 2015). "Bill Nighy: 'I'm greedy for beauty'". The Guardian. Archived from the original on March 23, 2017. Retrieved March 23, 2017.
73. ^ a b Drug Approved to Treat Hand-Crippling Syndrome Archived 2010-04-09 at the Wayback Machine, Delthia Ricks, Chicago Tribune, March 17, 2010.
74. ^ Spencer Leigh (2015). Frank Sinatra: An Extraordinary Life. McNidder and Grace Limited. ISBN 9780857160881. Retrieved 2020-01-18.
## External links[edit]
Classification
D
* ICD-10: M72.0
* ICD-9-CM: 728.6
* OMIM: 126900
* MeSH: D004387
* DiseasesDB: 4011
External resources
* MedlinePlus: 001233
* eMedicine: med/592 orthoped/81 plastic/299 pmr/42 derm/774
* Patient UK: Dupuytren's contracture
* v
* t
* e
Soft tissue disorders
Capsular joint
Synoviopathy
* Synovitis/Tenosynovitis
* Calcific tendinitis
* Stenosing tenosynovitis
* Trigger finger
* De Quervain syndrome
* Transient synovitis
* Ganglion cyst
* osteochondromatosis
* Synovial osteochondromatosis
* Plica syndrome
* villonodular synovitis
* Giant-cell tumor of the tendon sheath
Bursopathy
* Bursitis
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lower limb
* Iliotibial band syndrome
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other/general:
* Tendinitis/Tendinosis
Nonjoint
Fasciopathy
* Fasciitis: Plantar
* Nodular
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* Eosinophilic
Fibromatosis/contracture
* Dupuytren's contracture
* Plantar fibromatosis
* Aggressive fibromatosis
* Knuckle pads
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Dupuytren's contracture | c0013312 | 2,329 | wikipedia | https://en.wikipedia.org/wiki/Dupuytren%27s_contracture | 2021-01-18T18:53:57 | {"mesh": ["D004387"], "umls": ["C0013312"], "icd-9": ["728.6"], "icd-10": ["M72.0"], "wikidata": ["Q1330254"]} |
Colour anomaly, sometimes referred to as partial colour blindness, is an inherited condition in which people have full trichromatic colour vision, but do not make the same colour matches as the majority of the human population. It is much more common than dichromacy or other forms of colour blindness, affecting about 6% of human males in Northern European populations.[1] Two forms are common, known as protanomaly and deuteranomaly. In order to match a given spectral yellow light, protanomalous observers need more red light in a red/green mixture than the majority of observers, and deuteranomalous observers need more green. Tritanomaly, affecting mixtures involving blue, is much less common. Colour anomalies can be measured by an instrument called an anomaloscope, in which coloured lights are mixed in a controlled way; typical demonstration anomaloscopes are set up for measuring the red/green anomalies, but with appropriate choices of colours to mix, tritanomaly can also be measured.[2]
## References[edit]
1. ^ Deeb, Samir S. (2006). "Genetics of variation in human color vision and the retinal cone mosaic". Current Opinion in Genetics & Development. 16 (3): 301–307. doi:10.1016/j.gde.2006.04.002. PMID 16647849.
2. ^ Moreland, J.D.; Kerr, J. (1979). "Optimization of a Rayleigh-type equation for the detection of tritanomaly". Vision Research. 19 (12): 1369–1375. doi:10.1016/0042-6989(79)90209-8. PMID 316945.
* v
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Physiology of the visual system
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Pathways
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palsies
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Anopsia
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subjective
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Color topics
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Color science
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* Light
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* On Vision and Colours
* Metamerism
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Color perception
* Color vision
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* Achromatopsia
* test
* Tetrachromacy
* Color constancy
* Color term
* Color depth
* Color photography
* Spot color
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* Web colors
* Color mapping
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* The dress
Color psychology
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Color
philosophy
Color space
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* additive
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Color terms
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* Blue
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Cultural differences
* Linguistic relativity and the color naming debate
* Blue–green distinction in language
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Color dimensions
* Hue
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Color
organizations
* Pantone
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* International Colour Authority
* International Commission on Illumination (CIE)
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Lists
* List of colors: A–F
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Related
* Vision
* Digital image processing
* Multi-primary color display
* Quattron
* Qualia
* Lighting
* Local color (visual art)
* Category
* Index
This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Color anomaly | c4023316 | 2,330 | wikipedia | https://en.wikipedia.org/wiki/Color_anomaly | 2021-01-18T18:42:14 | {"umls": ["C4023316"], "wikidata": ["Q26739327"]} |
Actinic cheilitis
Other namesAtinic cheilosis,[1] Atinic keratosis of lip,[2] Solar cheilosis[2],Sailor's lip,[3] Farmer's lip[4]
Picture of Actinic Cheilitis. This is also known as sailor's lip or farmer's lip.
SpecialtyDermatology
Actinic cheilitis is cheilitis (lip inflammation) caused by long term sunlight exposure. Essentially it is a burn,[2] and a variant of actinic keratosis which occurs on the lip.[5] It is a premalignant condition,[6] as it can develop into squamous cell carcinoma (a type of mouth cancer).
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 5.1 Medication
* 5.2 Procedures
* 6 Epidemiology
* 7 References
* 8 External links
## Signs and symptoms[edit]
AC almost always affects the lower lip and only rarely the upper lip, probably because the lower lip is more exposed to the sun.[7] In the unusual cases reported where it affects the upper lip, this may be due to upper lip prominence.[7] The commissures (corners of the mouth) are not usually involved.[2][6]
Affected individuals may experience symptoms such as a dry sensation and cracking of the lips.[7] It is usually painless and persistent.
The appearance is variable. White lesions indicate hyperkeratosis.[7] Red, erosive or ulcerative lesions indicate atrophy, loss of epithelium and inflammation.[7] Early, acute lesions may be erythematous (red) and edematous (swollen).[2] With months and years of sun exposure, the lesion becomes chronic and may be grey-white in color and appear dry, scaly and wrinkled.[2]
There is thickening whitish discoloration of the lip at the border of the lip and skin. There is also a loss of the usually sharp border between the red of the lip and the normal skin, known as the vermillion border. The lip may become scaly and indurated as AC progresses.
When palpated, the lip may have a texture similar to rubbing the gloved finger along sandpaper.[7]
AC may occur with skin lesions of actinic keratosis or skin cancer elsewhere, particularly on the head and neck[6] since these are the most sun exposed areas. Rarely it may represent a genetic susceptibility to light damage (e.g. xeroderma pigmentosum or actinic prurigo).[2]
## Causes[edit]
AC is caused by chronic and excessive exposure to ultraviolet radiation in sunlight.
Risk factors include:
* Outdoor lifestyle: e.g. farmers, sailors, fishermen, windsurfers, mountaineers, golfers, etc.[2] This has given rise to synonyms for this condition such as "sailor's lip" and "farmer's lip".[8] The prevalence in agricultural workers in a semi-arid region of Brazil is reported to be 16.7%.[9]
* Light skin complexion: the condition typically affects individuals with lighter skin tones,[8] particularly Caucasians living in tropical regions.[2] In one report, 96% of persons with AC had phenotype II according to the Fitzpatrick scale.[10]
* Age: AC typically affects older individuals, and rarely those under the age of 45.[8]
* Gender: the condition affects males more commonly than females. Sometimes this ratio is reported as high as 10:1.[8]
Additional factors may also play a role, including tobacco use, lip irritation, poor oral hygiene, and ill-fitting dentures.[11]
## Diagnosis[edit]
Tissue biopsy is indicated.
## Prevention[edit]
To prevent AC from developing, protective measures could be undertaken such as avoiding mid-day sun,[2] or use of a broad-brimmed hat,[2] lip balm with anti UVA and UVB ingredients (e.g. para-aminobenzoic acid),[7] or sun blocking agents (e.g. zinc oxide, titanium oxide)[7] prior to sun exposure.
## Treatment[edit]
This condition is considered premalignant because it may lead to squamous cell carcinoma in about 10% of all cases. It is not possible to predict which cases will progress into SCC, so the current consensus is that all lesions should be treated.[12]
Treatment options include 5-fluorouracil, imiquimod, scalpel vermillionectomy, chemical peel, electrosurgery, and carbon dioxide laser vaporization. These curative treatments attempt to destroy or remove the damaged epithelium. All methods are associated with some degree of pain, edema, and a relatively low rate of recurrence.
### Medication[edit]
Topical 5-fluorouracil (5-FU, Efudex, Carac) has been shown to be an effective therapy for diffuse, but minor actinic cheilitis. 5-fluorouracil works by blocking DNA synthesis. Cells that are rapidly growing need more DNA, so they accumulate more 5-fluorouracil, resulting in their death. Normal skin is much less affected. The treatment usually takes 2–4 weeks depending on the response. The typical response includes an inflammatory phase, followed by redness, burning, oozing, and finally erosion. Treatment is stopped when ulceration and crusting appear. There is minimal scarring. Complete clearance has been reported in about 50% of patients.[13]
Imiquimod (Aldara) is an immune response modifier that has been studied for the treatment of actinic cheilitis. It promotes an immune response in the skin leading to apoptosis (death) of the tumor cells. It causes the epidermis to be invaded by macrophages, which leads to epidermal erosion. T-cells are also activated as a result of imiquimod treatment. Imiquimod appears to promote an “immune memory” that reduces the recurrence of lesions. There is minimal scarring. Complete clearance has been demonstrated in up to 45% of patients with actinic keratoses. However, the dose and duration of therapy, as well as the long-term efficacy, still need to be established in the treatment of actinic cheilitis.[5]
### Procedures[edit]
Both cryosurgery and electrosurgery are effective choices for small areas of actinic cheilitis. Cryosurgery is accomplished by applying liquid nitrogen in an open spraying technique. Local anesthesia is not required, but treatment of the entire lip can be quite painful. Cure rates in excess of 96% have been reported. Cryosurgery is the treatment of choice for focal areas of actinic cheilitis. Electrosurgery is an alternate treatment, but local anesthesia is required, making it less practical than cryosurgery. With both techniques, adjacent tissue damage can delay healing and promote scar formation.[11]
More extensive or recurring areas of actinic cheilitis may be treated with either a shave vermillionectomy or a carbon dioxide laser. The shave vemillionectomy removes a portion of the vermillion border but leaves the underlying muscle intact. Considerable bleeding can occur during the procedure due to the vascular nature of the lip. A linear scar may also form after treatment, but this can usually be minimized with massage and steroids. Healing time is short, and effectiveness is very high.[11]
A newer procedure uses a carbon dioxide laser to ablate the vermillion border. This treatment is relatively quick and easy to perform, but it requires a skilled operator. Anesthesia is usually required. Secondary infection and scarring can occur with laser ablation. In most cases, the scar is minimal, and responds well to steroids. Pain can be a progressive problem during the healing phase, which can last three weeks or more. However, the carbon dioxide laser also offers a very high success rate, with very few recurrences.[11]
Chemical peeling with 50% trichloroacetic acid has also been evaluated, but results have been poor. Healing usually takes 7–10 days with very few side effects. However, limited studies show that the success rate may be lower than 30%.[11]
## Epidemiology[edit]
It is a common condition.[8]
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ a b c d e f g h i j k Scully C (2013). Oral and Maxillofacial Medicine: The Basis of Diagnosis and Treatment. Elsevier Health Sciences. pp. 182–183. ISBN 978-0-7020-4948-4.
3. ^ Treister NS; Bruch JM (2010). Clinical oral medicine and pathology. New York: Humana Press. p. 121. ISBN 978-1-60327-519-4.
4. ^ Wenig BM (7 May 2012). Atlas of Head and Neck Pathology. Elsevier Health Sciences. pp. 331–332. ISBN 978-1-4557-3381-1.
5. ^ a b Larios, G; Alevizos, A; Rigopoulos, D (15 April 2008). "Recognition and treatment of actinic cheilitis". American Family Physician. 77 (8): 1078–9. PMID 18481555.
6. ^ a b c Lotti T; Parish LC; Rogers RS (6 December 2012). Oral Diseases: Textbook and Atlas. Springer Science & Business Media. pp. 228–229. ISBN 978-3-642-59821-0.
7. ^ a b c d e f g h Kolokythas A (21 October 2013). Lip Cancer: Treatment and Reconstruction. Springer Science & Business Media. pp. 12–16. ISBN 978-3-642-38180-5.
8. ^ a b c d e Chi AC; Damm DD; Neville BW; Allen CM; Bouquot J (11 June 2008). Oral and Maxillofacial Pathology. Elsevier Health Sciences. pp. 405–406. ISBN 978-1-4377-2197-3.
9. ^ Yardimci, G; Kutlubay, Z; Engin, B; Tuzun, Y (16 December 2014). "Precancerous lesions of oral mucosa". World Journal of Clinical Cases. 2 (12): 866–72. doi:10.12998/wjcc.v2.i12.866. PMC 4266835. PMID 25516862.
10. ^ Rossoe, EW; Tebcherani, AJ; Sittart, JA; Pires, MC (2011). "Actinic cheilitis: aesthetic and functional comparative evaluation of vermilionectomy using the classic and W-plasty techniques" (PDF). Anais Brasileiros de Dermatologia. 86 (1): 65–73. doi:10.1590/S0365-05962011000100008. PMID 21437524.
11. ^ a b c d e Dufresne, RG Jr; Curlin, MU (January 1997). "Actinic cheilitis. A treatment review". Dermatologic Surgery. 23 (1): 15–21. doi:10.1111/j.1524-4725.1997.tb00002.x. PMID 9107289.
12. ^ Berman, B; Bienstock, L; Kuritzky, L; Mayeaux, EJ Jr; Tyring, SK (May 2006). "Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel". The Journal of Family Practice. 55 (5): suppl 1–8. PMID 16672155.
13. ^ Richard A. Helms; Eric T. Herfindal; David J. Quan; Dick R. Gourley (2006). Textbook of Therapeutics: Drug and Disease Management. Lippincott Williams & Wilkins. p. 223. ISBN 978-0-7817-5734-8.
## External links[edit]
Classification
D
* ICD-10: L56.8
* ICD-9-CM: 692.72,692.74,692.82
* OMIM: 118330
* MeSH: C535669
* DiseasesDB: 32002
External resources
* eMedicine: article/1078725
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
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* Melanocytic nevus
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* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
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* Dens evaginatus
* Talon cusp
* Dentin dysplasia
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* Dilaceration
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* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
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* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
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* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
* v
* t
* e
Radiation-related disorders / Photodermatoses
Ultraviolet/ionizing
* Sunburn
* Phytophotodermatitis
* Solar urticaria
* Polymorphous light eruption
* Benign summer light eruption
* Juvenile spring eruption
* Acne aestivalis
* Hydroa vacciniforme
* Solar erythema
Non-ionizing
Actinic rays
* Actinic keratosis
* Atrophic actinic keratosis
* Hyperkeratotic actinic keratosis
* Lichenoid actinic keratosis
* Pigmented actinic keratosis
* Actinic cheilitis
* Actinic granuloma
* Actinic prurigo
* Chronic actinic dermatitis
Infrared/heat
* Erythema ab igne (Kangri ulcer
* Kairo cancer
* Kang cancer
* Peat fire cancer)
* Cutis rhomboidalis nuchae
* Poikiloderma of Civatte
Other
* Radiation dermatitis
* Acute
* Chronic radiodermatitis)
* Favre–Racouchot syndrome
* Photoaging
* Photosensitivity with HIV infection
* Phototoxic tar dermatitis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Actinic cheilitis | c0267026 | 2,331 | wikipedia | https://en.wikipedia.org/wiki/Actinic_cheilitis | 2021-01-18T18:30:06 | {"gard": ["9619"], "mesh": ["C535669"], "icd-9": ["692.74", "692.82", "692.72"], "icd-10": ["L56.8"], "wikidata": ["Q2514487"]} |
Bobble-head doll syndrome
SpecialtyNeurology
Bobble-head doll syndrome is a rare neurological movement disorder in which patients, usually children around age 3, begin to bob their head and shoulders forward and back, or sometimes side-to-side, involuntarily, in a manner reminiscent of a bobblehead doll. The syndrome is related to cystic lesions and swelling of the third ventricle in the brain. Symptoms of bobble-head doll syndrome are diverse but can be grouped into two categories: physical and neurological.[1] The most common form of treatment is surgical implanting of a shunt to relieve the swelling of the brain.[2]
## Contents
* 1 Signs and symptoms
* 1.1 Physical
* 1.2 Neurological
* 2 Pathophysiology
* 3 Diagnosis
* 3.1 Classification
* 4 Treatment
* 4.1 Removal of lesion
* 4.2 Ventriculoperitoneal shunt
* 4.3 Endoscopic ventriculocystocisternostomy
* 5 Prognosis
* 6 Epidemiology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
Bobble-head doll syndrome is first reported as a movement disorder in patients. However, after performing several tests and scans of the brain, the characteristic movement is found to be neurological in origin.
### Physical[edit]
The main physical symptom of bobble-head doll syndrome is the most obvious to diagnose and involves two to three bobs per second of the head, which can sometimes also include the shoulders and upper torso. The patient is unaware of the movements and unable to control them unless directed to stop or given simple mental tasks such as basic arithmetic or spelling words. However, once the task is completed by the patient, the bobbing tends to resume after about a minute. Thus, the bobbing is described by doctors as volitional, or able to be stopped by making a conscious decision.[3] The bobbing also disappears while the patient is asleep, a common feature of most movement disorders.
A supplemental symptom of the head bobbing is a presence of ataxia. Several patients were reported as having difficulty walking, running, and climbing steps because of the bobbing. It is likely that the constant bobbing has interrupted the patient’s ability to balance which requires input from several sources including the vestibular, ocular, somatosensory, and motor systems. Although the nature of these movements is physical, their source is neurological, generally stemming from a dysfunction of parts of the nervous system which control motor function.
### Neurological[edit]
A typical symptom in patients diagnosed with bobble-head doll syndrome is an enlargement of the head due to accumulation of cerebrospinal fluid in the third ventricle. This dilatation impairs communication between ventricles as well as the function of other surrounding structures.[4]
Quite often, the swelling is present along with cystic lesions in the third ventricle or surrounding periventricular structures. In reference to bobble-head doll syndrome, a third ventricular cystic lesion causes an obstruction in the foramina of Monro, which communicates with the lateral ventricles, and the proximal, cerebral aqueduct of Sylvius, which communicates with the fourth ventricle. It has also been reported to be caused by a cystic choroid plexus papilloma of the third ventricle and obstructive hydrocephalus. It is this blockage that is thought to produce the characteristic bobble-head movements.[5] Other patients have seen the onset of bobble-head doll syndrome from the presence of a suprasellar cyst in the arachnoid mater of the meninges. It, too, obstructs the foramen of Monro.[6]
## Pathophysiology[edit]
Those susceptible to acquiring bobble-head doll syndrome range from newborns to adults—with the oldest reported patient being 26 years old.[2] However, the majority of cases involve children who have yet to reach puberty.
Although the exact pathogenesis of bobble-head doll syndrome is still unknown, there are many theories as to how and why it does what it does. Most of these theories acknowledge the striking similarity of symptoms between bobble-head doll syndrome and other movement disorders.
The presence of cystic lesions, causing swelling in the third ventricle, is a common feature in all patients. It is this dilatation that causes pressure to be applied to the surrounding structures of the third ventricle, such as the diencephalon. It is possible that the back and forth movement of fluid within the cyst causes rhythmic pressure on the diencephalic motor pathways.[4] One of the key periventricular structures in that pathway is the thalamus which is responsible for relaying motor signals to the cerebral cortex as well as regulating consciousness, sleep, and alertness. The disappearance of the head movements while asleep implies that their origin may lie within the extrapyramidal system which is a part of the motor system that controls coordination of movement. The tracts associated with the extrapyramidal system are controlled by various structures of the central nervous system, such as the cerebellum and basal ganglia. The basal ganglia plays a large part in controlling motor function and thus, abnormalities to this system can result in movement disorders such as Parkinson’s Disease and dyskinesia, both of which share commonalities with bobble-head doll syndrome.[4]
The tic-like movements and swelling of the third ventricle associated with bobble-head doll syndrome are similar to that of other movement disorders caused by diseases of the corpus callosum and aforementioned basal ganglia. Because of the swelling, added pressure is applied to these formations causing their basic functions to be disturbed. Through pneumoencephalographic studies of patients with Parkinson’s, Huntington's, and dystonia musculorum deformans, it was discovered that, along with patients with bobble-head doll syndrome, a statistically significant swelling of the third ventricle existed. Thus, researchers believe that the connection between bobble-head doll syndrome and other movement disorders is that, in both, the movements are not caused by a particular lesion, but rather a hindrance of multiple neuronal structures or pathways. In the case of bobble-head doll syndrome, the disturbance is related to those structures proximal to the third ventricle.[3] More research is being conducted in order to find the neurophysiologic basis for bobble-head doll syndrome and its connection with other movement disorders, but with the rare occurrence of the disorder, progress is slow.[7]
Another theory exists behind the cause of bobble-head doll syndrome. It states that the constant head movements create a temporary relief in intraventricular obstruction by both shifting the cyst to the posterior—away from the foramina of Monro—and a reduction in cyst size. This points to the fact that the bobbing may be a “learned behavior” and a way to relieve the symptoms of hydrocephalus.[8]
## Diagnosis[edit]
Several methods exist for diagnosing a patient as having bobble-head doll syndrome. Most involve brain scans to look for swelling while some use cisternography to observe obstruction in cerebrospinal fluid (CSF) flow among ventricles.
In order to try to investigate the flow dynamics of the cerebrospinal fluid, doctors utilize cisternography, which injects a radiolabeled substance into the CSF via lumbar puncture. The CSF flow is then tracked by taking pictures at incremental times. However, cisternography is declining in use with physicians who are opting to use MRI instead, to assess CSF flow.[9]
Cerebrospinal fluid flow is important in diagnosing bobble-head doll syndrome because disturbances in CSF dynamics can be contributed to blockages in the connections between ventricles such as foramen and aqueducts. Such blockages are tell-tale signs that a cyst is present. Also, if CSF cannot flow freely, it will begin to accumulate leading to hydrocephalus. CSF is secreted by choroid plexuses located on the roofs of the ventricles. After travelling through each ventricle, the CSF leaves the fourth ventricle and flows around the brain stem, cerebellum, hemispheres, and finally, down into the subarachnoid space. To complete the cycle, the CSF then moves back up to the basal cisternae to start over. In patients with bobble-head doll syndrome, an impairment exists in the ability to reabsorb CSF by the arachnoid granulations leading to an accumulation.[8] Presently, doctors will utilize magnetic resonance imaging to get an image of the afflicted area. If swelling exists in the third ventricle along with cystic lesions, both of which are accompanied by the characteristic head bobbing, a diagnosis of bobble-head doll syndrome is likely. From here, the doctor will propose the available treatment options listed below.[7]
### Classification[edit]
Bobble-head doll syndrome does not have a precise classification in the major medical catalogs because of its rarity and complexity. Although it is a movement disorder, it is caused by neuronal obstruction of ventricle communication. Thus, it is grouped with hydrocephalus under the World Health Organization’s International Classification of Diseases (ICD) as G93.0, under ICD-10, and 348, under ICD-9.
## Treatment[edit]
No single cure exists because bobble-head doll syndrome can be caused by several compounding disorders. However, most times surgery will fully resolve the movement disorder. Successful surgical procedures include surgical removal of the lesion, insertion of a ventriculoperitoneal shunt, and ventriculocisternostomy.
### Removal of lesion[edit]
In the case of choroid plexus papilloma, surgical removal of the cyst-containing lesion from within the third ventricle caused a full recovery. The mobile nature of the cystic lesion led to its intermittent obstruction of the foramen of Monro and proximal aqueduct, producing the bobble-head symptoms. Once removed, all symptoms disappeared.[5]
### Ventriculoperitoneal shunt[edit]
Often, doctors will implant a shunt to reduce the intracranial pressure caused by the accumulation of CSF in the third ventricle. Typically, this will succeed in restricting the swelling and allowing proper flow of CSF. With this relief, the head bobbing will disappear and bobble-head doll syndrome will no longer be present.[2] However, in one case, after a year of shunt placement, the patient switched from forward-back bobbing to side-to-side swaying. There was no discernible reasoning for the switch found. A hypothesis emerged from this case that cerebellar malformations themselves can cause bobble-head doll syndrome.[1]
### Endoscopic ventriculocystocisternostomy[edit]
For those with suprasellar arachnoid cysts, it has been discovered that endoscopic ventriculocystocisternostomy is the optimal treatment option. By fenestrating, or opening, the cystic membrane and removing the fluid, all obstructions of the aqueduct were resolved. In patients receiving this treatment, a full recovery is the most common result.[6]
## Prognosis[edit]
Although surgery is agreed upon as the primary treatment option for patients suffering from bobble-head doll syndrome, surgical treatment has been reported to completely remove all symptoms in only half of the cases. Reason for this stems from late diagnoses which can significantly decrease the hope for a full recovery and lead to permanent profound obstructive hydrocephalus.[10] Thus, prognosis depends upon the time elapsed between the first signs of the disorder and the time of surgical treatment. Early diagnosis and treatment is highly important in successful treatment of bobble-head doll syndrome.[2]
## Epidemiology[edit]
The rarity of the syndrome is such that, since 1966, only 34 cases have been reported. Of those cases, the average onset of head bobbing is 3 years and 3 months old while surgical intervention occurred on average, at age 6 years and 11 months.[11]
## See also[edit]
* Hydrocephalus
* Movement disorder
* Dandy–Walker syndrome
## References[edit]
1. ^ a b De Brito Henriques, J. G., Wandeck Henriques, K. S., Pianettj, G., Fonseca, L. F., Cardoso, F., & Da Silva, M. C. (2007). Bobble-head doll syndrome associated with Dandy-Walker syndrome. Journal of Neurosurgery, 107(3), 248-250.
2. ^ a b c d Zamponi, N., Rychlicki, F., Trignani, R., Polonara, G., Ruggiero, M., & Cesaroni, E. (2005). Bobble head doll syndrome in a child with a third ventricular cyst and hydrocephalus. Childs Nervous System, 21(5), 350-354.
3. ^ a b Nellhaus, G. (1967). BOBBLE-HEAD DOLL SYNDROME - A TIC WITH A NEUROPATHOLOGIC BASIS. Pediatrics, 40(2), 250-&.
4. ^ a b c Benton J.W., Nellhaus G, Huttenlocher P.R., Ojemann R.G., Dodge P.R. (1966). The bobble-head doll syndrome: report of unique truncal tremor associated with third ventricular cyst and hydrocephalus in children. Neurology, 16(8), 725–729.
5. ^ a b Pollack, I. F., Schor, N. F., Martinez, A. J., & Towbin, R. (1995). BOBBLE-HEAD DOLL SYNDROME AND DROP ATTACKS IN A CHILD WITH A CYSTIC CHOROID-PLEXUS PAPILLOMA OF THE 3RD-VENTRICLE - CASE-REPORT. [Note]. Journal of Neurosurgery, 83(4), 729-732.
6. ^ a b Hagebeuk, E. E. O., Kloet, A., Grotenhuis, J. A., & Peeters, E. A. J. (2005). Bobble-head doll syndrome successfully treated with an endoscopic ventriculocystocisternostomy - Case report and review of the literature. Journal of Neurosurgery, 103(3), 253-259.
7. ^ a b De Brito Henriques, Jose Gilberto. Electronic Interview. 15 October 2009.
8. ^ a b Wiese, J. A., Gentry, L. R., & Menezes, A. H. (1985). Bobble-head doll syndrome: review of the pathophysiology and CSF dynamics. [Case Reports;; Review]. Pediatr Neurol, 1(6), 361-366.
9. ^ Parkinson, D. (1996). Bobble-head doll syndrome. Journal of Neurosurgery, 84(3), 538-538.
10. ^ Goikhman, I., Zelnik, N., & Peled, N. (1998). Bobble-head doll syndrome: A surgically treatable condition manifested as a rare movement disorder. Movement Disorders, 13(1), 192-194.
11. ^ Mussell, H. G., Dure, L. S., Percy, A. K., & Grabb, P. S. (1997). Bobble-head doll syndrome: Report of a case and review of the literature. Movement Disorders, 12(5), 810-814.
## External links[edit]
Classification
D
* ICD-10: G93.0
* ICD-9-CM: 348
* MeSH: C536241
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Bobble-head doll syndrome | c2931137 | 2,332 | wikipedia | https://en.wikipedia.org/wiki/Bobble-head_doll_syndrome | 2021-01-18T18:28:35 | {"gard": ["9731"], "mesh": ["C536241"], "umls": ["C2931137"], "icd-9": ["348"], "icd-10": ["G93.0"], "wikidata": ["Q1451507"]} |
A rare, indolent primary cutaneous B-cell lymphoma characterized by a solitary or grouped erythematous plaques or tumors, preferentially located on the head, neck or trunk region, and composed of centroblasts and centrocytes arranged in a follicular, diffuse, or mixed growth pattern. The lesions are smooth and typically do not ulcerate. The neoplastic cells express pan B cell markers and Bcl-6, and typically lack Bcl-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
| Primary cutaneous follicle center lymphoma | c1333171 | 2,333 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=178540 | 2021-01-23T17:20:11 | {"umls": ["C1333171", "C1631066"], "icd-10": ["C82.6"], "synonyms": ["PCFCL"]} |
For general learning disability, see Intellectual disability.
Range of neurodevelopmental conditions
"Slow learner" redirects here. For the collection of short stories by Thomas Pynchon, see Slow Learner.
Learning disability
Other namesLearning difficulties,[1][2] Developmental academic disorder,[3][4] Nonverbal learning disorder,[4] Developmental disorder of scholastic skills, unspecified,[4] Knowledge acquisition disability NOS,[4] Learning disability NOS,[4] Learning disorder NOS[4]
People at a Learning Disabilities Month event[5]
SpecialtyPsychiatry, Neurology
Disability
Theory and models
* Disability theory
* Ableism / Disablism
* Medical model
* Social model
Education
* Mainstreaming
* Individualized Education Program (IEP)
* Special needs
* Special school
* Special education
* Learning disability
Therapy
* Physical
* Occupational
* Speech
Societal implications
* Disability rights movement
* Inclusion
* Normalization
* People-first language
* Pejorative terms
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the Severely Handicapped
* Groups
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Disabled sports
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Culture
* Disability in the arts
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* * Disability
* Lists
* v
* t
* e
Learning disability, learning disorder, or learning difficulty (British English) is a condition in the brain that causes difficulties comprehending or processing information and can be caused by several different factors. Given the "difficulty learning in a typical manner", this does not exclude the ability to learn in a different manner. Therefore, some people can be more accurately described as having a "learning difference", thus avoiding any misconception of being disabled with a lack of ability to learn and possible negative stereotyping. In the United Kingdom, the term "learning disability" generally refers to an intellectual disability, while difficulties such as dyslexia and dyspraxia are usually referred to as "learning difficulties".[6]
While learning disability, learning disorder and learning difficulty are often used interchangeably, they differ in many ways. Disorder refers to significant learning problems in an academic area. These problems, however, are not enough to warrant an official diagnosis. Learning disability, on the other hand, is an official clinical diagnosis, whereby the individual meets certain criteria, as determined by a professional (such as a psychologist, psychiatrist, speech language pathologist, or pediatrician). The difference is in degree, frequency, and intensity of reported symptoms and problems, and thus the two should not be confused. When the term "learning disorder" is used, it describes a group of disorders characterized by inadequate development of specific academic, language, and speech skills.[7] Types of learning disorders include reading (dyslexia), arithmetic (dyscalculia) and writing (dysgraphia).[7]
The unknown factor is the disorder that affects the brain's ability to receive and process information. This disorder can make it problematic for a person to learn as quickly or in the same way as someone who is not affected by a learning disability. People with a learning disability have trouble performing specific types of skills or completing tasks if left to figure things out by themselves or if taught in conventional ways.
Individuals with learning disabilities can face unique challenges that are often pervasive throughout the lifespan. Depending on the type and severity of the disability, interventions, and current technologies may be used to help the individual learn strategies that will foster future success. Some interventions can be quite simplistic, while others are intricate and complex. Current technologies may require student training to be effective classroom supports. Teachers, parents, and schools can create plans together that tailor intervention and accommodations to aid the individuals in successfully becoming independent learners. A multi-disciplinary team frequently helps to design the intervention and to coordinate the execution of the intervention with teachers and parents.[8] This team frequently includes school psychologists, special educators, speech therapists (pathologists), occupational therapists, psychologists, ESL teachers, literacy coaches, and/or reading specialists.[9]
## Contents
* 1 Definition
* 1.1 United States and Canada
* 1.1.1 Legislation in the United States
* 1.1.2 Canada
* 1.2 United Kingdom
* 1.3 Japan
* 2 Effects
* 3 Causes
* 4 Diagnosis
* 4.1 IQ-achievement discrepancy
* 4.2 Response to intervention
* 4.3 Latino English language learners
* 4.4 Spanish-speaking ELL
* 4.5 Assessment
* 5 Types
* 5.1 By stage of information processing
* 5.2 By function impaired
* 5.2.1 Reading disorder (ICD-10 and DSM-IV codes: F81.0/315.00)
* 5.2.2 Disorder of written expression (ICD-10 and DSM-IV-TR codes 315.2)
* 5.2.3 Math disability (ICD-10 and DSM-IV codes F81.2-3/315.1)
* 5.2.4 Non ICD-10/DSM
* 6 Management
* 7 Society and culture
* 7.1 School laws
* 7.2 Critique of the medical model
* 7.3 Culture
* 7.4 Social roots of learning disabilities in the U.S.
* 8 Contrast with other conditions
* 9 References
* 10 Further reading
* 11 External links
## Definition[edit]
Representatives of organizations committed to the education and welfare of individuals with learning disabilities are known as National Joint Committee on Learning Disabilities (NJCLD).[10] The NJCLD used the term 'learning disability' to indicate a discrepancy between a child's apparent capacity to learn and his or her level of achievement.[11] Several difficulties existed, however, with the NJCLD standard of defining learning disability. One such difficulty was its belief of central nervous system dysfunction as a basis of understanding and diagnosing learning disability. This conflicted with the fact that many individuals who experienced central nervous system dysfunction, such as those with cerebral palsy, did not experience disabilities in learning. On the other hand, those individuals who experienced multiple handicapping conditions along with learning disability frequently received inappropriate assessment, planning, and instruction. The NJCLD notes that it is possible for learning disability to occur simultaneously with other handicapping conditions, however, the two should not be directly linked together or confused.[12]
In the 1980s, NJCLD, therefore, defined the term learning disability as:
> a heterogeneous group of disorders manifested by significant difficulties in the acquisition and use of listening, speaking, reading, writing, reasoning or mathematical abilities. These disorders are intrinsic to the individual and presumed to be due to Central Nervous System Dysfunction. Even though a learning disability may occur concomitantly with other handicapping conditions (e.g. sensory impairment, intellectual disability, social and emotional disturbance) or environmental influences (e.g. cultural differences, insufficient/inappropriate instruction, psychogenic factors) it is not the direct result of those conditions or influences.
The 2002 LD Roundtable produced the following definition:
> Concept of LD: Strong converging evidence supports the validity of the concept of specific learning disabilities (SLD). This evidence is particularly impressive because it converges across different indicators and methodologies. The central concept of SLD involves disorders of learning and cognition that are intrinsic to the individual. SLD are specific in the sense that these disorders each significantly affect a relatively narrow range of academic and performance outcomes. SLD may occur in combination with other disabling conditions, but they are not due primarily to other conditions, such as intellectual disability, behavioral disturbance, lack of opportunities to learn, or primary sensory deficits.[13][page needed][14]
The issue of defining learning disabilities has generated significant and ongoing controversy.[15] The term "learning disability" does not exist in DSM-IV, but it has been added to the DSM-5. The DSM-5 does not limit learning disorders to a particular diagnosis such as reading, mathematics, or written expression. Instead, it is a single diagnosis criterion describing drawbacks in general academic skills and includes detailed specifiers for the areas of reading, mathematics, and written expression.[16]
### United States and Canada[edit]
In the United States and Canada, the terms learning disability and learning disorder (LD) refer to a group of disorders that affect a broad range of academic and functional skills including the ability to speak, listen, read, write, spell, reason, organize information, and do math. People with learning disabilities generally have intelligence that is average or higher.[17]
#### Legislation in the United States[edit]
The Section 504 of the Rehabilitation Act 1973, effective May 1977, guarantees certain rights to people with disabilities, especially in the cases of education and work, such being in schools, colleges and university settings.[18]
The Individuals with Disabilities Education Act, formerly known as the Education for All Handicapped Children Act, is a United States federal law that governs how states and public agencies provide early intervention, special education and related services to children with disabilities. It addresses the educational needs of children with disabilities from birth to the age of 21.[19] Considered as a civil rights law, states are not required to participate.[citation needed]
#### Canada[edit]
In Canada, the first association in support of children with learning disabilities was founded in 1962 by a group of concerned parents. Originally called the Association for Children with Learning Disabilities, the Learning Disabilities Association of Canada – LDAC was created to provide awareness and services for individuals with learning disabilities, their families, at work, and the community. Since education is largely the responsibility of each province and territory in Canada, provinces and territories have jurisdiction over the education of individuals with learning disabilities, which allows the development of policies and support programs that reflect the unique multicultural, linguistic, and socioeconomic conditions of its area.[20]
### United Kingdom[edit]
In the UK, terms such as specific learning difficulty (SpLD), developmental dyslexia, developmental coordination disorder and dyscalculia are used to cover the range of learning difficulties referred to in the United States as "learning disabilities". In the UK, the term "learning disability" refers to a range of developmental disabilities or conditions that are almost invariably associated with more severe generalized cognitive impairment.[21] The Lancet defines 'learning disability' as a "significant general impairment in intellectual functioning acquired during childhood", and states that roughly one in 50 British adults have one.[22]
### Japan[edit]
In Japan, acknowledgement and support for students with learning disabilities has been a fairly recent development, and has improved drastically in the last[which?] decade. The first definition for learning disability was coined in 1999, and in 2001, the Enrichment Project for the Support System for Students with Learning Disabilities was established. Since then, there have been significant efforts to screen children for learning disabilities, provide follow-up support, and provide networking between schools and specialists.[23]
## Effects[edit]
The effects of having a learning disability or learning difference are not limited to educational outcomes: individuals with learning disabilities may experience social problems as well. Neuropsychological differences can affect the accurate perception of social cues with peers.[24] Researchers argue persons with learning disabilities not only experience negative effects as a result of their learning distinctions, but also as a result of carrying a stigmatizing label. It has generally been difficult to determine the efficacy of special education services because of data and methodological limitations. Emerging research suggests adolescents with learning disabilities experience poorer academic outcomes even compared to peers who began high school with similar levels of achievement and comparable behaviors.[25] It seems their poorer outcomes may be at least partially due to the lower expectations of their teachers; national data show teachers hold expectations for students labeled with learning disabilities that are inconsistent with their academic potential (as evidenced by test scores and learning behaviors).[26] It has been said that there is a strong connection between children with a learning disability and their educational performance.[27]
Many studies have been done to assess the correlation between learning disability and self-esteem. These studies have shown that an individual's self-esteem is indeed affected by his or her awareness of their learning disability. Students with a positive perception of their academic abilities generally tend to have higher self-esteem than those who do not, regardless of their actual academic achievement. However, studies have also shown that several other factors can influence self-esteem. Skills in non-academic areas, such as athletics and arts, improve self-esteem. Also, a positive perception of one's physical appearance has also been shown to have positive effects of self-esteem. Another important finding is that students with learning disabilities are able to distinguish between academic skill and intellectual capacity. This demonstrates that students who acknowledge their academic limitations but are also aware of their potential to succeed in other intellectual tasks see themselves as intellectually competent individuals, which increases their self-esteem.[28]
Research involving individuals with learning disabilities who exhibit challenging behaviors who are subsequently treated with antipsychotic medications provides little evidence that any benefits outweigh the risk.[29]
## Causes[edit]
The causes for learning disabilities are not well understood, and sometimes there is no apparent cause for a learning disability. However, some causes of neurological impairments include:
Heredity and genetics
Learning disabilities are often linked through genetics and run in the family. Children who have learning disabilities often have parents who have the same struggles. Children of parents who had less than 12 years of school are more likely to have a reading disability. Some children have spontaneous mutations (i.e. not present in either parent) which can cause developmental disorders including learning disabilities.[30] One study[31] estimated that about one in 300 children had such spontaneous mutations, for example a fault in the CDK13 gene which is associated with learning and communication difficulties in the children affected.[32]
Problems during pregnancy and birth
A learning disability can result from anomalies in the developing brain, illness or injury. Risk factors are fetal exposure to alcohol or drugs and low birth weight (3 pounds or less). These children are more likely to develop a disability in math or reading. Children who are born prematurely, late, have a longer labor than usual, or have trouble receiving oxygen are more likely to develop a learning disability.[30]
Accidents after birth
Learning disabilities can also be caused by head injuries, malnutrition, or by toxic exposure (such as heavy metals or pesticides).[33][34]
## Diagnosis[edit]
### IQ-achievement discrepancy[edit]
Learning disabilities can be identified by psychiatrists, speech language pathologists, school psychologists, clinical psychologists, counseling psychologists, neuropsychologists, speech language pathologists, and other learning disability specialists through a combination of intelligence testing, academic achievement testing, classroom performance, and social interaction and aptitude. Other areas of assessment may include perception, cognition, memory, attention, and language abilities. The resulting information is used to determine whether a child's academic performance is commensurate with his or her cognitive ability. If a child's cognitive ability is much higher than his or her academic performance, the student is often diagnosed with a learning disability. The DSM-IV and many school systems and government programs diagnose learning disabilities in this way (DSM-IV uses the term "disorder" rather than "disability").
Although the discrepancy model has dominated the school system for many years, there has been substantial criticism of this approach among researchers.[35][36] Recent research has provided little evidence that a discrepancy between formally measured IQ and achievement is a clear indicator of LD.[37] Furthermore, diagnosing on the basis of a discrepancy does not predict the effectiveness of treatment. Low academic achievers who do not have a discrepancy with IQ (i.e. their IQ scores are also low) appear to benefit from treatment just as much as low academic achievers who do have a discrepancy with IQ (i.e. their IQ scores are higher than their academic performance would suggest).
Since 1998 there have been attempts to create a reference index more useful than IQ to generate predicted scores on achievement tests. For example, for a student whose vocabulary and general knowledge scores matches his/her reading comprehension score a teacher could assume that reading comprehension can be supported through work in vocabulary and general knowledge. If the reading comprehension score is lower in the appropriate statistical sense it would be necessary to first rule out things like vision problems[38]
### Response to intervention[edit]
Much current research has focused on a treatment-oriented diagnostic process known as response to intervention (RTI). Researcher recommendations for implementing such a model include early screening for all students, placing those students who are having difficulty into research-based early intervention programs, rather than waiting until they meet diagnostic criteria. Their performance can be closely monitored to determine whether increasingly intense intervention results in adequate progress.[37] Those who respond will not require further intervention. Those who do not respond adequately to regular classroom instruction (often called "Tier 1 instruction") and a more intensive intervention (often called "Tier 2" intervention) are considered "non-responders." These students can then be referred for further assistance through special education, in which case they are often identified with a learning disability. Some models of RTI include a third tier of intervention before a child is identified as having a learning disability.
A primary benefit of such a model is that it would not be necessary to wait for a child to be sufficiently far behind to qualify for assistance.[39] This may enable more children to receive assistance before experiencing significant failure, which may, in turn, result in fewer children who need intensive and expensive special education services. In the United States, the 2004 reauthorization of the Individuals with Disabilities Education Act permitted states and school districts to use RTI as a method of identifying students with learning disabilities. RTI is now the primary means of identification of learning disabilities in Florida.
The process does not take into account children's individual neuropsychological factors such as phonological awareness and memory, that can inform design instruction. By not taking into account specific cognitive processes, RTI fails to inform educators about a students' relative strengths and weaknesses[40] Second, RTI by design takes considerably longer than established techniques, often many months to find an appropriate tier of intervention. Third, it requires a strong intervention program before students can be identified with a learning disability. Lastly, RTI is considered a regular education initiative and consists of members of general education teachers, in conjunction with other qualified professionals.[8] Occupational therapists (OT's) in particular can support students in the educational setting by helping children in academic and non-academic areas of school including the classroom, recess and meal time. They can provide strategies, therapeutic interventions, suggestions for adaptive equipment, and environmental modifications. OT's can work closely with the child's teacher and parents to facilitate educational goals specific to each child under an RTI and/or IEP.[8]
### Latino English language learners[edit]
Demographers in the United States report that there has been a significant increase in immigrant children in the United States over the past two decades.[41] This information is vital because it has been and will continue to affect both students and how educators approach teaching methods. Various teaching strategies are more successful for students that are linguistic or culturally diverse versus traditional methods of teaching used for students whose first language is English. It is then also true that the proper way to diagnose a learning disability in English language learners (ELL) differs. In the United States, there has been a growing need to develop the knowledge and skills necessary to provide effective school psychological services, specifically for those professionals who work with immigrant populations.[42]
Currently, there are no standardized guidelines for the process of diagnosing English language learners (ELL) with specific learning disabilities (SLD). This is a problem since many students will fall through the cracks as educators are unable to clearly assess if a student's delay is due to a language barrier or true learning disability. With an unclear diagnosis, many students will suffer because they will not be provided with the tools they need to succeed in the public education school system. For example, in many occasions teachers have suggested retention or have taken no action at all when they lack experience working with English language learners. Students were commonly pushed toward testing, based on an assumption that their poor academic performance or behavioral difficulties indicated a need for special education.[43] Linguistically responsive psychologist understand that second language acquisition is a process and they understand how to support ELLs' growth in language and academically.[44] When ELLs are referred for a psychoeducational assessment, it is difficult to isolate and disentangle what are the effects of the language acquisition process, from poor quality educational services, from what may be academic difficulties that result from processing disorders, attention problems, and learning disabilities.[43] Additionally not having trained staff and faculty becomes more of an issue when staff is unaware of numerous types of psychological factors that immigrant children in the U.S dealing could be potentially dealing with. These factors that include acculturation, fear and/or worry of deportation, separation from social supports such as parents, language barriers, disruptions in learning experiences, stigmatization, economic challenge, and risk factors associated with poverty.[45][46] In the United States, there are no set policies mandating that all districts employ bilingual school psychologist, nor are schools equipped with specific tools and resources to assist immigrant children and families. Many school districts do not have the proper personnel that is able to communicate with this population.[47][page needed]
### Spanish-speaking ELL[edit]
A well trained bilingual school psychologist will be able to administer and interpret assessment all psychological testing tool. Also, an emphasis is placed on informal assessment measures such as language samples, observations, interviews, and rating scales as well as curriculum-based measurement to complement information gathered from formal assessments.[46][48] A compilation of these tests is used to assess whether an ELL student has a learning disability or merely is academically delayed because of language barriers or environmental factors. It is very unfortunate that many schools do not have school psychologist with the proper training nor access to appropriate tools. Also, many school districts frown upon taking the appropriate steps to diagnosing ELL students.
### Assessment[edit]
Many normed assessments can be used in evaluating skills in the primary academic domains: reading, including word recognition, fluency, and comprehension; mathematics, including computation and problem solving; and written expression, including handwriting, spelling and composition.
The most commonly used comprehensive achievement tests include the Woodcock-Johnson IV (WJ IV), Wechsler Individual Achievement Test II (WIAT II), the Wide Range Achievement Test III (WRAT III), and the Stanford Achievement Test–10th edition. These tests include measures of many academic domains that are reliable in identifying areas of difficulty.[37]
In the reading domain, there are also specialized tests that can be used to obtain details about specific reading deficits. Assessments that measure multiple domains of reading include Gray's Diagnostic Reading Tests–2nd edition (GDRT II) and the Stanford Diagnostic Reading Assessment. Assessments that measure reading subskills include the Gray Oral Reading Test IV – Fourth Edition (GORT IV), Gray Silent Reading Test, Comprehensive Test of Phonological Processing (CTOPP), Tests of Oral Reading and Comprehension Skills (TORCS), Test of Reading Comprehension 3 (TORC-3), Test of Word Reading Efficiency (TOWRE), and the Test of Reading Fluency. A more comprehensive list of reading assessments may be obtained from the Southwest Educational Development Laboratory.[49]
The purpose of assessment is to determine what is needed for intervention, which also requires consideration of contextual variables and whether there are comorbid disorders that must also be identified and treated, such as behavioral issues or language delays.[37] These contextual variables are often assessed using parent and teacher questionnaire forms that rate the students' behaviors and compares them to standardized norms.
However, caution should be made when suspecting the person with a learning disability may also have dementia, especially as people with Down's syndrome may have the neuroanatomical profile but not the associated clinical signs and symptoms.[50] Examination can be carried out of executive functioning as well as social and cognitive abilities but may need adaptation of standardized tests to take account of special needs.[51][52][53][54]
## Types[edit]
Learning disabilities can be categorized by either the type of information processing affected by the disability or by the specific difficulties caused by a processing deficit.
### By stage of information processing[edit]
Learning disabilities fall into broad categories based on the four stages of information processing used in learning: input, integration, storage, and output.[55] Many learning disabilities are a compilation of a few types of abnormalities occurring at the same time, as well as with social difficulties and emotional or behavioral disorders.[56]
Input
This is the information perceived through the senses, such as visual and auditory perception. Difficulties with visual perception can cause problems with recognizing the shape, position, or size of items seen. There can be problems with sequencing, which can relate to deficits with processing time intervals or temporal perception. Difficulties with auditory perception can make it difficult to screen out competing sounds in order to focus on one of them, such as the sound of the teacher's voice in a classroom setting. Some children appear to be unable to process tactile input. For example, they may seem insensitive to pain or dislike being touched.
Integration
This is the stage during which perceived input is interpreted, categorized, placed in a sequence, or related to previous learning. Students with problems in these areas may be unable to tell a story in the correct sequence, unable to memorize sequences of information such as the days of the week, able to understand a new concept but be unable to generalize it to other areas of learning, or able to learn facts but be unable to put the facts together to see the "big picture." A poor vocabulary may contribute to problems with comprehension.
Storage
Problems with memory can occur with short-term or working memory, or with long-term memory. Most memory difficulties occur with one's short-term memory, which can make it difficult to learn new material without more repetitions than usual. Difficulties with visual memory can impede learning to spell.
Output
Information comes out of the brain either through words, that is, language output, or through muscle activity, such as gesturing, writing or drawing. Difficulties with language output can create problems with spoken language. Such difficulties include answering a question on demand, in which one must retrieve information from storage, organize our thoughts, and put the thoughts into words before we speak. It can also cause trouble with written language for the same reasons. Difficulties with motor abilities can cause problems with gross and fine motor skills. People with gross motor difficulties may be clumsy, that is, they may be prone to stumbling, falling, or bumping into things. They may also have trouble running, climbing, or learning to ride a bicycle. People with fine motor difficulties may have trouble with handwriting, buttoning shirts, or tying shoelaces.
### By function impaired[edit]
Deficits in any area of information processing can manifest in a variety of specific learning disabilities. It is possible for an individual to have more than one of these difficulties. This is referred to as comorbidity or co-occurrence of learning disabilities.[57] In the UK, the term dual diagnosis is often used to refer to co-occurrence of learning difficulties.
#### Reading disorder (ICD-10 and DSM-IV codes: F81.0/315.00)[edit]
Reading disorder is the most common learning disability.[58] Of all students with specific learning disabilities, 70–80% have deficits in reading. The term "Developmental Dyslexia" is often used as a synonym for reading disability; however, many researchers assert that there are different types of reading disabilities, of which dyslexia is one. A reading disability can affect any part of the reading process, including difficulty with accurate or fluent word recognition, or both, word decoding, reading rate, prosody (oral reading with expression), and reading comprehension. Before the term "dyslexia" came to prominence, this learning disability used to be known as "word blindness."
Common indicators of reading disability include difficulty with phonemic awareness—the ability to break up words into their component sounds, and difficulty with matching letter combinations to specific sounds (sound-symbol correspondence).
#### Disorder of written expression (ICD-10 and DSM-IV-TR codes 315.2)[edit]
Further information: Disorder of written expression
The DSM-IV-TR criteria for a disorder of written expression is writing skills (as measured by a standardized test or functional assessment) that fall substantially below those expected based on the individual's chronological age, measured intelligence, and age-appropriate education, (Criterion A). This difficulty must also cause significant impairment to academic achievement and tasks that require composition of written text (Criterion B), and if a sensory deficit is present, the difficulties with writing skills must exceed those typically associated with the sensory deficit, (Criterion C).[59]
Individuals with a diagnosis of a disorder of written expression typically have a combination of difficulties in their abilities with written expression as evidenced by grammatical and punctuation errors within sentences, poor paragraph organization, multiple spelling errors, and excessively poor penmanship. A disorder in spelling or handwriting without other difficulties of written expression do not generally qualify for this diagnosis. If poor handwriting is due to an impairment in the individuals' motor coordination, a diagnosis of developmental coordination disorder should be considered.
By a number of organizations, the term "dysgraphia" has been used as an overarching term for all disorders of written expression.
#### Math disability (ICD-10 and DSM-IV codes F81.2-3/315.1)[edit]
Further information: Dyscalculia
Sometimes called dyscalculia, a math disability involves difficulties such as learning math concepts (such as quantity, place value, and time), difficulty memorizing math facts, difficulty organizing numbers, and understanding how problems are organized on the page. Dyscalculics are often referred to as having poor "number sense".[60]
#### Non ICD-10/DSM[edit]
* Nonverbal learning disability: Nonverbal learning disabilities often manifest in motor clumsiness, poor visual-spatial skills, problematic social relationships, difficulty with mathematics, and poor organizational skills. These individuals often have specific strengths in the verbal domains, including early speech, large vocabulary, early reading and spelling skills, excellent rote memory and auditory retention, and eloquent self-expression.[61]
* Disorders of speaking and listening: Difficulties that often co-occur with learning disabilities include difficulty with memory, social skills and executive functions (such as organizational skills and time management).
## Management[edit]
Spell checkers are one tool for managing learning disabilities.
Interventions include:
* Mastery model:
* Learners work at their own level of mastery.
* Practice
* Gain fundamental skills before moving onto the next level
* Note: this approach is most likely to be used with adult learners or outside the mainstream school system.
* Direct instruction:[62]
* Emphasizes carefully planned lessons for small learning increments
* Scripted lesson plans
* Rapid-paced interaction between teacher and students
* Correcting mistakes immediately
* Achievement-based grouping
* Frequent progress assessments
* Classroom adjustments:
* Special seating assignments
* Alternative or modified assignments
* Modified testing procedures
* Quiet environment
* Special equipment:
* Word processors with spell checkers and dictionaries
* Text-to-speech and speech-to-text programs
* Talking calculators
* Books on tape
* Computer-based activities
* Classroom assistants:
* Note-takers
* Readers
* Proofreaders
* Scribes
* Special education:
* Prescribed hours in a resource room
* Placement in a resource room[63]
* Enrollment in a special school or a separate classroom in a regular school[64] for learning disabled students
* Individual education plan (IEP)
* Educational therapy
Sternberg[65] has argued that early remediation can greatly reduce the number of children meeting diagnostic criteria for learning disabilities. He has also suggested that the focus on learning disabilities and the provision of accommodations in school fails to acknowledge that people have a range of strengths and weaknesses, and places undue emphasis on academic success by insisting that people should receive additional support in this arena but not in music or sports. Other research has pinpointed the use of resource rooms as an important—yet often politicized component of educating students with learning disabilities.[66]
## Society and culture[edit]
### School laws[edit]
Schools in the United States have a legal obligation to new arrivals to the country, including undocumented students. The landmark Supreme Court ruling Plyler v. Doe (1982) grants all children, no matter their legal status, the right to a free education.[67][68] This ruling suggests that as a country we acknowledge that we have a population of students with specific needs that differ from those of native speakers. Additionally specifically in regards to ELL's the supreme court ruling Lau v. Nichols (1974) stated that equal treatment in school did not mean equal educational opportunity.[69] Thus if a school teaches a lesson in a language that students do not understand then they are effectively worthless. This ruling is also supported by English language development services provided in schools, but unfortunately, these rulings do not require the individuals that teach and provide services to have any specific training nor is licensing different from a typical teacher or services provider.
### Critique of the medical model[edit]
Learning disability theory is founded in the medical model of disability, in that disability is perceived as an individual deficit that is biological in origin.[70][71] Researchers working within a social model of disability assert that there are social or structural causes of disability or the assignation of the label of disability, and even that disability is entirely socially constructed.[71][72][73][74][75] Since the turn of the 19th century, education in the United States has been geared toward producing citizens who can effectively contribute to a capitalistic society, with a cultural premium on efficiency and science.[76][77] More agrarian cultures, for example, do not even use learning ability as a measure of adult adequacy,[78][79] whereas the diagnosis of learning disabilities is prevalent in Western capitalistic societies because of the high value placed on speed, literacy, and numeracy in both the labor force and school system.[80][81][82]
### Culture[edit]
There are three patterns that are well known in regards to mainstream students and minority labels in the United States:
* "A higher percentage of minority children than of white children are assigned to special education";
* "within special education, white children are assigned to less restrictive programs than are their minority counterparts";
* "the data — driven by inconsistent methods of diagnosis, treatment, and funding — make the overall system difficult to describe or change”.[83]
In the present day, it has been reported that white districts have more children from minority backgrounds enrolled in special education than they do majority students. “It was also suggested that districts with a higher percentage of minority faculty had fewer minority students placed in special education suggesting that 'minority students are treated differently in predominantly white districts than in predominantly minority districts'".[84]
Educators have only recently started to look into the effects of culture on learning disabilities.[85] If a teacher ignores a student's culturally diverse background, the student will suffer in the class. “The cultural repertoires of students from cultural learning disorder backgrounds have an impact on their learning, school progress, and behavior in the classroom”.[86] These students may then act out and not excel in the classroom and will, therefore, be misdiagnosed: “Overall, the data indicates that there is a persistent concern regarding the misdiagnosis and inappropriate placement of students from diverse backgrounds in special education classes since the 1975”.[87]
### Social roots of learning disabilities in the U.S.[edit]
Learning disabilities have a disproportionate identification of racial and ethnic minorities and students who have low socioeconomic status (SES). While some attribute the disproportionate identification of racial/ethnic minorities to racist practices or cultural misunderstanding,[88][89] others have argued that racial/ethnic minorities are overidentified because of their lower status.[90][91] Similarities were noted between the behaviors of “brain-injured” and lower class students as early as the 1960s.[72] The distinction between race/ethnicity and SES is important to the extent that these considerations contribute to the provision of services to children in need. While many studies have considered only one characteristic of the student at a time,[92] or used district- or school-level data to examine this issue, more recent studies have used large national student-level datasets and sophisticated methodology to find that the disproportionate identification of African American students with learning disabilities can be attributed to their average lower SES, while the disproportionate identification of Latino youth seems to be attributable to difficulties in distinguishing between linguistic proficiency and learning ability.[93][94] Although the contributing factors are complicated and interrelated, it is possible to discern which factors really drive disproportionate identification by considering a multitude of student characteristics simultaneously. For instance, if high SES minorities have rates of identification that are similar to the rates among high SES Whites, and low SES minorities have rates of identification that are similar to the rates among low SES Whites, we can know that the seemingly higher rates of identification among minorities result from their greater likelihood to have low SES. Summarily, because the risk of identification for White students who have low SES is similar to that of Black students who have low SES, future research and policy reform should focus on identifying the shared qualities or experiences of low SES youth that lead to their disproportionate identification, rather than focusing exclusively on racial/ethnic minorities.[93][94] It remains to be determined why lower SES youth are at higher risk of incidence, or possibly just of identification, with learning disabilities.
## Contrast with other conditions[edit]
People with an IQ lower than 70 are usually characterized as having an intellectual disability and are not included under most definitions of learning disabilities because their difficulty in learning are considered to be related directly to their overall low intelligence.
Attention-deficit hyperactivity disorder (ADHD) is often studied in connection with learning disabilities, but it is not actually included in the standard definitions of learning disabilities. An individual with ADHD may struggle with learning, but he or she can often learn adequately once successfully treated for the ADHD. A person can have ADHD but not learning disabilities or have learning disabilities without having ADHD. The conditions can co-occur.[95]
People diagnosed with ADHD sometimes have impaired learning. Some of the struggles people with ADHD have might include lack of motivation, high levels of anxiety, and the inability to process information.[96] There are studies that suggest people with ADHD generally have a positive attitude toward academics and, with developed study skills, can perform just as well as individuals without learning disabilities. Also, using alternate sources of gathering information, such as websites, study groups, and learning centers, can help a person with ADHD be academically successful.[96]
Some research is beginning to make a case for ADHD being included in the definition of LDs since it is being shown to have a strong effect on "executive functions" required for learning. This has not as yet affected any official definitions. Though, historically, ADHD was not clearly distinguished from other disabilities related to learning.[citation needed] Scientific research continues to explore the traits, struggles, and learning styles of those with ADHD.
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## Further reading[edit]
* Barr, S.; Eslami, Z.; Joshi, R.M. (2012). "Core strategies to support English language learners". The Educational Forum. 76: 105–117. doi:10.1080/00131725.2011.628196. S2CID 143509969.
* Garcia-Joslin, J.J.; Carrillo, G.L.; Guzman, V.; Vega, D.; Plotts, C.A.; Lasser, J. (2016). "Latino immigration: Preparing school psychologists to meet students' needs". School Psychology Quarterly. 31 (2): 256–269. doi:10.1037/spq0000136. PMID 26551253.
* Helman, A. L.; Calhoon, M.B.; Kern, L. (2015). "Improving science vocabulary of high school English language learners with reading disabilities". Learning Disability Quarterly. 38 (1): 40–52. doi:10.1177/0731948714539769. S2CID 145520140.
* Keller-Margulis, M.; Payan, A.; Jaspers, K.E.; Brewton, C. (2016). "Validity and diagnostic accuracy of written expression curriculum-based measurement for students with diverse language backgrounds". Reading & Writing Quarterly: Overcoming Learning Difficulties. 32 (2): 174–198. doi:10.1080/10573569.2014.964352. S2CID 146790684.
* Rodríguez, James L.; Cadiero-Kaplan, Karen (2008). "Bilingualism & Biliteracy: Issues of Equity, Access, & Social Justice for English Language Learners: Introduction to This Special Issue". Equity & Excellence in Education. 41 (3): 275–278. doi:10.1080/10665680802179139. S2CID 143725571.
* O'Bryon, E.C.; Rogers, M.R. (2010). "Bilingual school psychologists' assessment practices with English language learners". Psychology in the Schools. 47 (10): 1018–1034. doi:10.1002/pits.20521.
* Rodríguez Silva, L.H.; Roehr-Brackin, K. (2016). "Perceived learning difficulty and actual performance: Explicit and implicit knowledge of L2 English grammar points among instructed adult learners" (PDF). Studies in Second Language Acquisition. 38 (2): 317–340. doi:10.1017/S0272263115000340.
* Wagner, R.K.; Francis, D.J.; Morris, R.D. (2005). "Identifying English Language Learners with Learning Disabilities: Key Challenges and Possible Approaches". Learning Disabilities Research & Practice. 20 (1): 6–15. doi:10.1111/j.1540-5826.2005.00115.x.
* Rodis, P., Garrod, A., & Boscardin, M. L. (Eds.). (2001). Learning Disabilities & Life Stories. Boston, USA: Allan & Bacon.
* "Learning Difficulties Australia, www.ldaustralia.org, June 2008" (PDF).
## External links[edit]
Classification
D
* ICD-10: F81.9
* ICD-9-CM: 315.0-315.3
* MeSH: D007859
* DiseasesDB: 4509
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*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
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*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
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*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Learning disability | c0751265 | 2,334 | wikipedia | https://en.wikipedia.org/wiki/Learning_disability | 2021-01-18T18:48:33 | {"mesh": ["D007859"], "umls": ["C0751265", "C0023186"], "icd-9": ["315.0", "315.3"], "wikidata": ["Q860740"]} |
A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-24 (MCPH24) is caused by homozygous mutation in the NUP37 gene (609264) on chromosome 12q23. One such family has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Clinical Features
Braun et al. (2018) reported 3 brothers, born of consanguineous Pakistani parents (family PN-2), with congenital microcephaly (-5 to -8 SD), mildly impaired intellectual development, cerebellar vermis hypoplasia, and fifth finger clinodactyly. Additional clinical details were limited, but none had evidence of renal abnormalities.
Inheritance
The transmission pattern of MCPH24 in the family reported by Braun et al. (2018) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 3 brothers, born of consanguineous Pakistani parents (family PN-2), with MCPH24, Braun et al. (2018) identified a homozygous nonsense mutation in the NUP37 gene (R306X; 609264.0001). The mutation, which was found by high-throughput exon sequencing and confirmed by Sanger sequencing and homozygosity mapping, segregated with the disorder in the family. Patient fibroblasts showed significant differences from controls, including a lower number of nuclear pores, altered chromatin organization and nucleolar morphology, and widened and irregular perinuclear spaces with bulbous invasions of the nuclear envelope. Additional in vitro studies showed that mutant fibroblasts had decreased cellular proliferation rates compared to controls.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly, congenital (-5 to -8 SD) SKELETAL Hands \- Fifth finger clinodactyly NEUROLOGIC Central Nervous System \- Impaired intellectual development, mild \- Cerebellar vermis hypoplasia MISCELLANEOUS \- Onset at birth \- One consanguineous Pakistani family has been reported (last curated November 2018) MOLECULAR BASIS \- Caused by mutation in the nucleoporin, 37-kD gene (NUP37, 609264.0001 ) ▲ 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
| MICROCEPHALY 24, PRIMARY, AUTOSOMAL RECESSIVE | None | 2,335 | omim | https://www.omim.org/entry/618179 | 2019-09-22T15:43:16 | {"omim": ["618179"], "orphanet": ["93213"], "synonyms": ["Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis"]} |
Gaucher disease (GD) is a lysosomal storage disorder encompassing three main forms (types 1, 2 and 3), a fetal form and a variant with cardiac involvement (Gaucher disease - ophthalmoplegia - cardiovascular calcification or Gaucher-like disease).
## Epidemiology
The prevalence is approximately 1/100,000. The annual incidence of GD in the general population is about 1/60,000, but it can reach up to 1/1,000 in Ashkenazi Jewish populations.
## Clinical description
The clinical manifestations of this disease are highly variable. GD type 1 (90% of cases) is the chronic and non-neurological form associated with organomegaly (spleen, liver), bone anomalies (pain, osteonecrosis, pathological fractures) and cytopenia. Type 2, the acute neurological form, is characterized by early onset, rapidly progressing brainstem dysfunction, associated with organomegaly and leading to death before the age of 2. Type 3, the subacute neurological form, affects children or adolescents and is characterized by progressive encephalopathy (oculomotor apraxia, epilepsy and ataxia) with the systemic manifestations seen in type 1. The fetal form manifests with a decrease or absence of fetal movements or anasarca. Gaucher-like disease presents with progressive calcification of the aorta and the aortic and/ or mitral valves as its main feature.
## Etiology
GD is due to mutations in the GBA gene (1q21) that codes for a lysosomal enzyme, glucocerebrosidase, or in very rare cases the PSAP gene that codes for its activator protein (saposin C). The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramide (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, the spleen and the bone marrow (Gaucher cells).
## Diagnostic methods
Formal diagnosis of the disease is determined by the measurement of glucocerebrosidase levels in circulating leukocytes. Genotyping confirms the diagnosis.
## Differential diagnosis
Differential diagnoses include other lysosomal storage disorders. The presence of Gaucher-like cells can be found in certain hematologic diseases (lymphoma, Hodgkin's lymphoma and chronic lymphocytic leukemia; see these terms).
## Genetic counseling
Transmission is autosomal recessive.
## Management and treatment
There are two available treatments for GD type 1 and 3: enzyme substitution therapy (using imiglucerase or velaglucerase) and substrate reduction therapy (miglustat). These treatments are ineffective for GD type 2.
## Prognosis
The prognosis is good in GD type 1. In type 2, death usually occurs before the age of 2. Without specific treatment, GD type 3 progresses to death within a few years.
*[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
| Gaucher disease | c0017205 | 2,336 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=355 | 2021-01-23T18:58:58 | {"gard": ["8233"], "mesh": ["D005776"], "omim": ["230800", "230900", "231000", "231005", "608013", "610539"], "umls": ["C0017205"], "icd-10": ["E75.2"], "synonyms": ["Acid beta-glucosidase deficiency", "Glucocerebrosidase deficiency"]} |
Blue diaper syndrome
Other namesOther Names: Hypercalcemia, familial, with nephrocalcinosis and indicanuria
Blue diaper syndrome has an autosomal recessive pattern of inheritance.
Medicationnone
Blue diaper syndrome is a rare, autosomal recessive metabolic disorder characterized in infants by bluish urine-stained diapers. It is also known as Drummond's syndrome, and hypercalcemia.[1]
It is caused by a defect in tryptophan absorption. Bacterial degradation of unabsorbed tryptophan in the intestine leads to excessive indole production and thus to indicanuria which, on oxidation to indigo blue, causes a peculiar bluish discoloration of the diaper (indoluria). Symptoms typically include digestive disturbances, fever and visual problems. Some may also develop disease due to the incomplete breakdown of tryptophan.[2]
It was characterized in 1964, and is associated with the X linked sex gene.[3]
Since this syndrome is X linked, the chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms.[4] Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”.[2] Parents can undergo genetic testing to see if their child will get this syndrome, but most do not find out until they see the symptoms mentioned below.[4]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 References
* 6 External links
## Signs and symptoms[edit]
The signs and symptoms of blue diaper syndrome may include irritability, constipation, poor appetite, vomiting, and poor growth. Some children experience frequent fevers and intestinal infections.[1][2]
Hypercalcemia could be a potential issue in affected children. Some children with blue diaper syndrome have eye or vision issues, particularly underdeveloped portions of the eye, including the cornea and optic disc.
## Genetics[edit]
Blue diaper syndrome affects males and females equally. The number of people affected in the general population is unknown.[1]
Blue diaper syndrome is thought to be inherited as an autosomal recessive disorder.
Recent research indicates that mutations in the LAT2[5] and TAT1[6] genes might be involved in causing this syndrome.
It is linked to X linked gene and in order for a person to develop it, both parents must carry the gene.[2] This syndrome is diagnosed through clinical evaluation and a fresh urine sample [2]
## Diagnosis[edit]
A diagnosis is usually made through clinical evaluation, observing detailed patient history then identifying the possible characteristic symptoms and testing fresh urine samples to enhance such evidence.[1]
## Treatment[edit]
Children with blue diaper syndrome are put on restricted diets. This is in effort to reduce kidney damage. Restrictions include: calcium, protein, vitamin D, and tryptophan. Calcium is restricted to help prevent kidney damage.[2] Examples of food with high levels of tryptophan include turkey and milk.[2] Diets are also expected to be low in protein, which will help prevent symptoms, along with restricting vitamin D intake.
Antibiotics may be used to control or eliminate particular intestinal bacteria.
Genetic counseling can also be beneficial, as well as taking part in clinical trials.[7]
## References[edit]
1. ^ a b c d "Blue Diaper Syndrome - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2016-03-01.
2. ^ a b c d e f g "Blue Diaper Syndrome - NORD (National Organization for Rare Disorders)".
3. ^ Drummond KN, Michael AF, Ulstrom RA, Good RA (1964). "The blue diaper syndrome: Familial hypercalcemia with nephrocalcinosis and indicanuria; A new familial disease, with definition of the metabolic abnormality". Am J Med. 37 (6): 928–48. doi:10.1016/0002-9343(64)90134-2. PMID 14246093.
4. ^ a b "Blue Diaper Syndrome disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org.
5. ^ Park SY, Kim JK, Kim IJ, Choi BK, Jung KY, Lee S, Park KJ, Chairoungdua A, Kanai Y, Endou H, Kim do K (2005). "Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule". Arch Pharm Res. 28 (4): 421–32. doi:10.1007/BF02977671. PMID 15918515. S2CID 2139640.
6. ^ Kim do K, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H (2002). "The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location". Genomics. 79 (1): 95–103. doi:10.1006/geno.2001.6678. PMID 11827462.
7. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Blue diaper syndrome". www.orpha.net.
## External links[edit]
Classification
D
* OMIM: 211000
* MeSH: C536239
* DiseasesDB: 33872
External resources
* Orphanet: 94086
* Blue diaper syndrome at NIH's Office of Rare Diseases
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Blue diaper syndrome | c0268478 | 2,337 | wikipedia | https://en.wikipedia.org/wiki/Blue_diaper_syndrome | 2021-01-18T18:34:59 | {"gard": ["5939"], "mesh": ["C536239"], "umls": ["C0268478"], "orphanet": ["94086"], "wikidata": ["Q503458"]} |
Speech delay, also known as alalia, refers to a delay in the development or use of the mechanisms that produce speech.[1] Speech – as distinct from language – is the actual process of making sounds, using such organs and structures as the lungs, vocal cords, mouth, tongue, teeth, etc. Language delay refers to a delay in the development or use of the knowledge of language.
Because language and speech are two independent stages, they may be individually delayed. For example, a child may be delayed in speech (i.e., unable to produce intelligible speech sounds), but not delayed in language. In this case, the child would be attempting to produce an age appropriate amount of language, but that language would be difficult or impossible to understand. Conversely, since a child with a language delay typically has not yet had the opportunity to produce speech sounds, it is likely to have a delay in speech as well.
## Contents
* 1 Signs and symptoms
* 2 Effects
* 3 Causes
* 4 Therapies and treatments
* 5 See also
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
The warning signs of early speech delay are categorized into age-related milestones, beginning at the age of 12 months and continuing through early adolescence.[2][3]
At the age of 12 months, there is cause for concern if the child is not able to do the following:
* Using gestures such as waving good-bye and pointing at objects
* Practicing the use of several different consonant sounds[2][3]
* Vocalizing or communicating needs[2][3]
Between the ages of 15 and 18 months children are at a higher risk for speech delay if they are displaying the following:
* Not saying "momma" and "dada"
* Not reciprocating when told "no", "hello", and "bye"[2][3]
* Does not have a one to three word vocabulary at 12 months and up to 15 words by 18 months
* Is unable to identify body parts[2][3]
* Displaying difficulties imitating sounds and actions[2]
* Shows preference to gestures over verbalization[2]
Additional signs of speech delay after the age of 2 years and up to the age of 4 include the following:
* Inability to spontaneously produce words and phrases[2][3]
* Inability to follow simple directions and commands[2][3]
* Cannot make two word connections[2][3]
* Lacks consonant sounds at the beginning or end of words[2][3]
* Is difficult to understand by close family members[2][3]
* Is not able to display the tasks of common household objects[2][3]
* Is unable to form simple 2 to 3 word sentences
## Effects[edit]
Studies show that children diagnosed with speech delay are more likely to present with behavioral and social emotional problems both in childhood and as adults. Decreased receptive language, reading, and learning skills are common side effects for children that suffer from a speech delay and do not receive adequate intervention.[4] Similar studies suggest that children with speech delays are more likely to have a difficult time communicating and bonding with peers, which could have negative effects on their psychosocial health later in life.[4]
## Causes[edit]
At times, speech delay and impairment is caused by a physical disruption in the mouth such as a deformed frenulum, lips, or palate. If the motion or ability to form words and appropriate sounds is disrupted, the child may be slow to pick up words and lack the ability to shape their mouth and tongue in the formation of words.[5]
Other more serious concerns are those that can be caused by oral-motor issues.[2][6] Oral-motor dysfunction refers to a lack or delay in the area of the brain that speech is formed and created and communicated to the mouth and tongue.[2] While speech may be the only concern, this disorder can be highlighted with feeding issues as well.[7]
Children that are having speech delay disorders could have the following characteristics (Shriberg 1982):
* Speech mechanism in which speech is associated with hearing, motor speech and craniofacial malfunction
* Cognitive-linguistic aspects in which the impairment is associated with the child's intellectual, receptive, expressive and linguistic ability.
* Psychosocial issues in which the impairment is associated with caregiver, school environment, and the child's self behaviors such as aggression and maturity[1]
The many other causes of speech delay include bilingual children with phonological disorders,[8] autism spectrum conditions, childhood apraxia,[9] auditory processing disorder, prematurity, cognitive impairment[10] and hearing loss.[2][5] In addition, when children are addicted to screens, they aren’t stimulated to be involved in conversations, causing speech delays.[11][unreliable source?] Broomfield and Dodd's (2004a)[full citation needed] found out after survey that 6.4% of children who are perfectly normal showed speech difficulty while they lacked these disorders will often show early signs and are at times identified as "at risk" when the speech delay is diagnosed.
## Therapies and treatments[edit]
After the initial diagnosis of speech delay, a hearing test will be administered to ensure that hearing loss or deafness is not an underlying cause of the delay.[6] If a child has successfully completed the hearing test, the therapy or therapies used will be determined. There are many therapies available for children that have been diagnosed with a speech delay, and for every child, the treatment and therapies needed vary with the degree, severity, and cause of the delay. While speech therapy is the most common form of intervention, many children may benefit from additional help from occupational and physical therapies as well. Physical and occupational therapies can be used for a child that is suffering from speech delay due to physical malformations and children that have also been diagnosed with a developmental delay such as autism or a language processing delay. Music therapy has effective results in the fundamentals of speech development, including phonological memory, sentence understanding, sentence memory, and morphological rule generation.[12] Children that have been identified with hearing loss can be taught simple sign language to build and improve their vocabulary in addition to attending speech therapy.
The parents of a delayed child are the first and most important tool in helping overcome the speech delay.[3][4] The parent or caregiver of the child can provide the following activities at home, in addition to the techniques suggested by a speech therapist, to positively influence the growth of speech and vocabulary:
* Reading to the child regularly[2][3][4]
* Use of questions and simple, clear language[5][6]
* Positive reinforcement in addition to patience[2][3][4]
For children that are suffering from physical disorder that is causing difficulty forming and pronouncing words, parents and caregivers suggest using and introducing different food textures to exercise and build jaw muscles while promoting new movements of the jaw while chewing. Another less studied technique used to combat and treat speech delay is a form of therapy using music to promote and facilitate speech and language development.[13] It is important to understand that music therapy is in its infancy and has yet to be thoroughly studied and practiced on children suffering from speech delays and impediments.[13]
## See also[edit]
Syndromes or disorders
* Auditory processing disorder
* Developmental coordination disorder
* Developmental verbal dyspraxia
* Down syndrome
* Speech sound disorder
* Lists of language disorders
General topics
* Bilingualism
* Cleft palate
* Cluttering
* Language acquisition
* Psycholinguistics
## References[edit]
1. ^ a b Dodd, Barbara (2013). Differential Diagnosis and Treatment of Children with Speech Disorder. John Wiley & Sons. p. 8. ISBN 978-1118713341.
2. ^ a b c d e f g h i j k l m n o p q r Nelsen, Amy. "Delayed Speech or Language Development". Retrieved 12 April 2012.
3. ^ a b c d e f g h i j k l m n babycenter. "Warning signs of a toddler's language delay". Retrieved 12 April 2012.
4. ^ a b c d e Mann, Denise. "Speech Delay in Kids Linked to Later Emotional Problems". Retrieved 2012-04-22.
5. ^ a b c University of Michigan. "Speech and Language Delay and Disorder". Retrieved 2012-04-22.
6. ^ a b c Keep Kids Healthy. "Speech Delay". Retrieved 2012-04-22.
7. ^ . p. 8. Missing or empty `|title=` (help)
8. ^ Dodd, Barbara (2013). Differential Diagnosis and Treatment of Children with Speech Disorder. Johan Wiley & Sons. p. 275. ISBN 978-1118713341.
9. ^ Dodd, Barbara (2013). Differential Diagnosis and Treatment of Children with Speech Disorder. John Wiley & Sons. p. 211. ISBN 978-1118713341.
10. ^ Dodd, Barbara (2013). Differential Diagnosis and Treatment of Children with Speech Disorder. John Wiley & Songs. p. 244. ISBN 978-1118713341.
11. ^ Clarke, Kelly (2015). "Your Wrong Parenting May Lead to Speech Delay in Children". Khaleej Times.
12. ^ Gross, Wibke; Ostermann, Thomas; Linden, Ulrike (2010). "Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study". BMC Complementary and Alternative Medicine. 10: 39. doi:10.1186/1472-6882-10-39. PMC 2921108. PMID 20663139.
13. ^ a b Grob, Wibke; Ulrike Linden; Thomas Ostermann (21 July 2010). "Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study". BMC Complement Altern Med. 10: 39. doi:10.1186/1472-6882-10-39. PMC 2921108. PMID 20663139.
## Further reading[edit]
* Kennison, S. M. (2013). Introduction to Language Development. Los Angeles, CA: Sage.
## External links[edit]
* American Speech-Language-Hearing Association (ASHA): Different Issues in Speech and Language Development.
* KidsHealth:Delay in Speech and Language
* Early Identification of Speech-Language Delays and Disorders
* The Listen Up Web-Language Development
* YourChild: Speech and Language Delays and Disorders University of Michigan Health System
Look up alalia in Wiktionary, the free dictionary.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Speech delay | c0241210 | 2,338 | wikipedia | https://en.wikipedia.org/wiki/Speech_delay | 2021-01-18T18:53:29 | {"mesh": ["D007805"], "umls": ["C0241210"], "wikidata": ["Q2301465"]} |
B-cell lymphoma
Micrograph showing a large B cell lymphoma. Field stain.
SpecialtyHematology, oncology
The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.
B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.[1]
Prognosis and treatment depends on the specific type of lymphoma as well as the stage and grade. Treatment includes radiation and chemotherapy. Early-stage indolent B-cell lymphomas can often be treated with radiation alone, with long-term non-recurrence. Early-stage aggressive disease is treated with chemotherapy and often radiation, with a 70-90% cure rate.[1] Late-stage indolent lymphomas are sometimes left untreated and monitored until they progress. Late-stage aggressive disease is treated with chemotherapy, with cure rates of over 70%.[1]
## Contents
* 1 Types
* 1.1 Common
* 1.2 Rare
* 1.3 Other
* 2 Workup
* 3 Associated chromosomal translocations
* 4 See also
* 5 References
* 6 External links
## Types[edit]
Micrograph showing Hodgkin's lymphoma, a type of B cell lymphoma that is usually considered separate from other B cell lymphomas. Field stain.
CT scan of primary B cell lymphoma in the left ilium, as diffuse cortical and trabecular thickening of the hemipelvis, mimicking Paget's disease.[2]
There are numerous kinds of lymphomas involving B cells. The most commonly used classification system is the WHO classification, a convergence of more than one, older classification systems.
### Common[edit]
Five account for nearly three out of four patients with non-Hodgkin lymphoma:[3]
* Diffuse large B-cell lymphoma (DLBCL)[4]
* Follicular lymphoma
* Marginal zone B-cell lymphoma (MZL) or mucosa-associated lymphatic tissue lymphoma (MALT)
* Small lymphocytic lymphoma (SLL, also known as chronic lymphocytic leukemia, CLL)
* Mantle cell lymphoma (MCL)
### Rare[edit]
The remaining forms are much less common:[3]
* DLBCL variants or sub-types of
* Primary mediastinal (thymic) large B cell lymphoma
* T cell/histiocyte-rich large B-cell lymphoma
* Primary cutaneous diffuse large B-cell lymphoma, leg type (Primary cutaneous DLBCL, leg type)
* EBV positive diffuse large B-cell lymphoma of the elderly
* Diffuse large B-cell lymphoma associated with chronic inflammation
* Fibrin-associated diffuse large B-cell lymphoma
* Primary testicular diffuse large B-cell lymphoma
* Burkitt's lymphoma
* Lymphoplasmacytic lymphoma, which may manifest as Waldenström's macroglobulinemia
* Nodal marginal zone B cell lymphoma (NMZL)
* Splenic marginal zone lymphoma (SMZL)
* Intravascular lymphomas variants
* Intravascular large B-cell lymphoma
* Intravascular NK-cell lymphoma
* Intravascular T-cell lymphoma
* Primary effusion lymphoma
* Lymphomatoid granulomatosis
* Primary central nervous system lymphoma
* ALK+ large B-cell lymphoma
* Plasmablastic lymphoma
* Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease
* B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
* B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma
### Other[edit]
Additionally, some researchers separate out lymphomas that appear to result from other immune system disorders, such as AIDS-related lymphoma.
Classic Hodgkin's lymphoma and nodular lymphocyte predominant Hodgkin's lymphoma are now considered forms of B-cell lymphoma.[5]
## Workup[edit]
When a person appears to have a B-cell lymphoma, the main components of a workup (for determining the appropriate therapy and the person's prognosis) are:[6]
* Establishing the precise subtype: Initially, an incisional or excisional biopsy is preferred. A core needle biopsy is discouraged except in case a lymph node is not easily accessible. Fine-needle aspiration is only acceptable in selected circumstances, in combination with immunohistochemistry and flow cytometry.
* Determining the extent of the disease (localized or advanced; nodal or extranodal)
* The person's general health status.
Main immunohistochemistry markers in common types of B-cell lymphoma.[7] Follicular lymphoma Marginal zone B-cell lymphoma (MZL) or mucosa-associated lymphatic tissue lymphoma (MALT) Small lymphocytic lymphoma (SLL) / chronic lymphocytic leukemia (CLL) Mantle cell lymphoma (MCL)
CD5 \- \- \+ \+
CD10 \+ \- \- \-
CD23 \- \- \+ \-
Cyclin D1 \- \- \- \+
## Associated chromosomal translocations[edit]
Chromosomal translocations involving the immunoglobulin heavy locus (IGH@) is a classic cytogenetic abnormality for many B-cell lymphomas, including follicular lymphoma, mantle cell lymphoma and Burkitt's lymphoma. In these cases, the immunoglobulin heavy locus forms a fusion protein with another protein that has pro-proliferative or anti-apoptotic abilities. The enhancer element of the immunoglobulin heavy locus, which normally functions to make B cells produce massive production of antibodies, now induces massive transcription of the fusion protein, resulting in excessive pro-proliferative or anti-apoptotic effects on the B cells containing the fusion protein.
In Burkitt's lymphoma and mantle cell lymphoma, the other protein in the fusion is c-myc (on chromosome 8) and cyclin D1[8] (on chromosome 11), respectively, which gives the fusion protein pro-proliferative ability. In follicular lymphoma, the fused protein is Bcl-2 (on chromosome 18), which gives the fusion protein anti-apoptotic abilities.
## See also[edit]
* Richter's transformation
* T-cell lymphoma
## References[edit]
1. ^ a b c Merck Manual home edition, Non-Hodgkin Lymphomas
2. ^ Nguyen, Nghi; Khan, Mujahid; Shah, Muhammad (2017). "Primary B-cell lymphoma of the pelvic bone in a young patient: Imaging features of a rare case". Cancer Research Frontiers. 3 (1): 51–55. doi:10.17980/2017.51. ISSN 2328-5249.
3. ^ a b "The Lymphomas" (PDF). The Leukemia & Lymphoma Society. May 2006. p. 12. Archived from the original (PDF) on 2008-07-06. Retrieved 2008-04-07.
4. ^ Mazen Sanoufa; Mohammad Sami Walid; Talat Parveen (2010). "B-Cell Lymphoma of the Thoracic Spine Presenting with Spinal Cord Pressure Syndrome". Journal of Clinical Medicine Research. 2 (1): 53–54. doi:10.4021/jocmr2010.02.258w. PMC 3299178. PMID 22457704.
5. ^ "HMDS: Hodgkin's Lymphoma". Archived from the original on 4 March 2009. Retrieved 2009-02-01.
6. ^ Mohammad Muhsin Chisti, Haresh Kumar, Sumeet K Yadav. "B-Cell Lymphoma Workup". Medscape.CS1 maint: multiple names: authors list (link) Updated Jul 27, 2020
7. ^ Attanoos, Richard (2018). "Lymphoid Malignancies of the Pleura and Peritoneum": 203–208. doi:10.1017/9781316402009.016. Cite journal requires `|journal=` (help)
8. ^ Li JY, Gaillard F, Moreau A, et al. (May 1999). "Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridization". Am. J. Pathol. 154 (5): 1449–52. doi:10.1016/S0002-9440(10)65399-0. PMC 1866594. PMID 10329598.
## External links[edit]
Classification
D
* ICD-10: C85.1
* ICD-O: 9680/0, 9699/3, 9699/3
* MeSH: D016393
External resources
* eMedicine: med/1358
* Overview and video at harvard.edu
* Lymphoma Association – Specialist UK charity providing free information and support to patients, their families, friends and carers
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* t
* e
Leukaemias, lymphomas and related disease
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(lymphoma,
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(most CD19
* CD20)
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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
| B-cell lymphoma | c0079731 | 2,339 | wikipedia | https://en.wikipedia.org/wiki/B-cell_lymphoma | 2021-01-18T18:37:09 | {"gard": ["5877"], "mesh": ["D016393"], "umls": ["C1332362"], "icd-10": ["C85.1"], "wikidata": ["Q4833719"]} |
Pes anserine bursitis
Pes anserine is on the lower right side of image (Pes anserine bursa lies beneath)
SpecialtyOrthopedic
Pes anserine bursitis is an inflammatory condition of the medial (inner) knee at the anserine bursa, a sub muscular bursa, just below the pes anserinus.
## Contents
* 1 Pathology
* 1.1 Pathophysiology
* 1.2 Muscles involved
* 2 Diagnosis
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Pathology[edit]
The pes anserinus is the insertion of the conjoined tendons sartorius, gracilis, and semitendinosus into the anteromedial proximal tibia. Theoretically, bursitis results from stress to this area (e.g. stress may result when an obese individual with anatomic deformity from arthritis ascends or descends stairs). An occurrence of pes anserine bursitis commonly is characterized by pain, especially when climbing stairs, tenderness, and local swelling.[1]
### Pathophysiology[edit]
The etymology of the name relates to the insertion of the conjoined tendons into the anteromedial proximal tibia. From anterior to posterior, the pes anserinus is made up of the tendons of the sartorius, gracilis, and semitendinosus muscles. The tendon's name, which literally means "goose's foot," was inspired by the pes anserinus's webbed, footlike structure. The conjoined tendon lies superficial to the tibial insertion of the medial collateral ligament (MCL) of the knee.[citation needed]
### Muscles involved[edit]
* Sartorius aids in knee and hip flexion, as in sitting or climbing; abducts and laterally rotates thigh; innervated by the femoral nerve.[2]
* Gracilis adducts the hip; flexes and medially rotates tibia at knee; innervated by the obturator nerve.[2]
* Semitendinosus flexes knee; medially rotates tibia on femur when knee is flexed; medially rotates femur when hip is extended; counteracts forward bending at hips; innervated by tibial nerve and common fibular nerve.[2]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (February 2019)
## Treatment[edit]
Pes anserine bursitis can be treated with a variety of physical therapy treatments, steroids to reduce inflammation, or surgery if necessary. Physical therapy treatments include therapeutic ultrasound, electrical stimulation (E-stim), rehabilitative exercises, and ice.[1] Therapeutic ultrasound and E-stim deliver medication deep to the bursa to reduce inflammation. The rehabilitative exercises are done with the intention of stretching and strengthening the hip abductors, quadriceps, and hamstrings.[1] These stretches have the potential to significantly reduce the tension over the pes anserine bursa.[citation needed]
## See also[edit]
* Anserine bursa
* Bursitis
* Pes anserinus
## References[edit]
1. ^ a b c Glencross, P. Mark (20 January 2017). "Pes Anserine Bursitis". Medscape. WebMD LLC. Retrieved 3 May 2018.
2. ^ a b c K. Saladin, Anatomy & Physiology 5th Edition, 2010, McGraw-Hill.
## External links[edit]
Classification
D
External resources
* eMedicine: article/308694
* v
* t
* e
Soft tissue disorders
Capsular joint
Synoviopathy
* Synovitis/Tenosynovitis
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Mechanism
Acute
Plasma-derived mediators
* Bradykinin
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* coagulation
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Tests
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General
* Lymphadenopathy
* List of inflammed body part states
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Pes anserine bursitis | None | 2,340 | wikipedia | https://en.wikipedia.org/wiki/Pes_anserine_bursitis | 2021-01-18T18:32:28 | {"umls": ["CL1378544"], "wikidata": ["Q7171312"]} |
Oguchi disease is an autosomal recessive retinal disorder characterized by congenital stationary night blindness (see this term) and the Mizuo-Nakamura phenomenon.
## Epidemiology
Oguchi disease is a very rare condition with approximately 50 cases described in the literature to date. It was originally discovered in Japan where the prevalence is the highest but has been found occasionally in European, American, Pakistani and Indian patients.
## Clinical description
The disease is characterized by congenital stationary night blindness and the Mizuo-Nakamura phenomenon which is a unique morphological and functional abnormality of the retina that presents with a typical golden-yellow or silver-gray discoloration of the fundus in the presence of light that disappears after dark-adaptation and appears again after the onset of light. Patients have non progressive night blindness since young childhood with normal day vision, but they often claim improvement of light sensitivities when they remain a long time in a dark environment. Eye fundus shows the Mizuo-Nakamura phenomenon as the only fundus feature. A prolonged dark adaptation of 3 hours or more leads to disappearance of the Mizuo-Nakamura phenomenon fundus changes. No evidence of spicules, macular changes or chorioretinal atrophy is observed. Normal visual acuity, normal caliber of retinal blood vessels and usually normal cone response on electroretinogram (ERG) recording suggest retinal dysfunction rather than degeneration.
## Etiology
Oguchi disease is caused by mutations in the SAG gene coding for arrestin located on chromosome 2q37(Oguchi type 1) or by mutations in the GRK1 gene that codes for the rhodopsin kinase located on the chromosome 13q34 (Oguchi type 2). Remarkably, some mutations in the SAG gene are associated with Oguchi disease and retinitis pigmentosa (RP) in the same family. Some mutations in SAG lead to RP.
## Diagnostic methods
The diagnosis is clinical and is based on the presence of night blindness and the observation of the Mizuo-Nakamura phenomenon by funduscopy and electroretinography (ERG). The clinical diagnosis is confirmed by genetic testing.
## Differential diagnosis
The differential diagnosis includes Stargardt disease, RP in female carriers, juvenile retinoschisis, and progressive cone dystrophy (see these terms). All these conditions may have fundus changes but without the classical Mizuo-Nakamura phenomenon.
## Genetic counseling
Oguchi disease is an autosomal recessive condition. Brothers and sisters of an affected case have a 25% risk to be also affected.
## Management and treatment
To date, there is not a specific treatment for Oguchi disease.
## Prognosis
In Oguchi disease the visual prognosis is good in absence of progression of symptoms. Although Oguchi disease is categorized as a stationary condition it can lead to reduced visual acuity or constricted visual fields, especially in older patients.
*[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
| Oguchi disease | c1306122 | 2,341 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=75382 | 2021-01-23T18:17:31 | {"gard": ["10118"], "mesh": ["C537743"], "omim": ["258100", "613411"], "umls": ["C1306122"], "icd-10": ["H53.6"], "synonyms": ["Congenital stationary night blindness, Oguchi type", "Oguchi syndrome"]} |
Inflammation of the paranasal sinuses due to fungal infection
Fungal sinusitis
Aspergillus is responsible in 90% of cases of fungal sinusitis
SpecialtyPulmonology
SymptomsFacial pain[1]
TypesInvasive, Non-invasive[1]
Diagnostic methodCT scan, MRI[1]
TreatmentSurgical(Management depends on which type)[1]
Fungal sinusitis is the inflammation of the lining mucosa of the paranasal sinuses due to fungal infection.[1] It occurs in people with reduced immunity. The maxillary sinus is the most commonly involved. Fungi responsible for fungal sinusitis are Aspergillus fumigatus (90%), Aspergillus flavus, and Aspergillus niger. Fungal sinusitis occurs most commonly in middle-aged populations. Diabetes mellitus is the most common risk factor involved.[2]
## Contents
* 1 Types
* 2 Signs and symptoms
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 Epidemiology
* 7 See also
* 8 References
* 9 Further reading
* 10 External links
## Types[edit]
Granuloma[3]
The types of fungal sinusitis are based on invasive and non-invasive as follows:[4][5]
* Invasive
* Acute fulminant
* Chronic invasive
* Granulomatous
* Non Invasive
* Saprophytic infection
* Sinus fungal ball
* Eosinophil related FRS including AFRS
## Signs and symptoms[edit]
Individuals with the condition of fungal sinusitis mostly present with features that include facial pain and pain around the eyes, nasal congestion, rhinorrhea(running nose), headache, later there may be ophthalmoplegia (paralysis of ocular muscles).[1]
## Pathophysiology[edit]
The mechanism of fungal sinusitis depends on which form, such as:
* Acute fulminant form – the fungus invades into vessels causing thrombosis, necrosis with minimum inflammation [3]
* Chronic invasive – fungal hyphae invades tissue leaving necrosis with minimal inflammation [3]
* Granulomatous form – invasive hyphae invades tissue with inflammation and non-caseating granuloma (with foreign bodies).[3]
* Saprophytic infection – growth of fungus seen on mucous crusts within sinus cavity.[3]
* Sinus fungal ball – sequestration of fungal hyphae as densely tangled, and has gritty matted appearance.[3]
* Eosinophil related Allergic fungal sinusitis – though not completely understood, a possible mechanism sees the protein component of fungus elicits IgE mediated allergic mucosal inflammation.[6]
## Diagnosis[edit]
In terms of diagnosis, the clinical examination gives an idea about fungal sinusitis,[5] as well as:
MRI
* Suggestive clinical features include - multiple recurrent episodes, persistent pathology, and absent ability to smell (the Eustachian tube may also be affected).[5]
* X Ray \- can be done if the diagnosis is not certain.[5]
* CT – can document the presence of sinusitis, in the coronal views[1]
* MRI – used to find the CNS spread (extent of the disease), to evaluate individuals who demonstrate signs of invasive fungal sinusitis [1]
* Histology studies[1]
## Treatment[edit]
Voriconazole
Treatment for fungal sinusitis can include surgical debridement; helps by slowing progression of disease thus allowing time for recovery[7] additionally we see the options below:
* In cases where the fungus has invaded the sinus tissue, echinocandins, oral voriconazole, and I.V amphoterecin may be used[8]
* For allergic fungal sinusitis, systemic corticosteroids like prednisolone, methylprednisolone are added for their anti-inflammatory effect, bronchodilators and expectorants help to clear secretions in the sinuses.[medical citation needed]
## Epidemiology[edit]
Though it is widely held that fungal infections of the nose and paranasal sinuses are not common, most agree that their frequency has been increasing over past decades.[9]
## See also[edit]
* Granuloma
## References[edit]
1. ^ a b c d e f g h i "Fungal Sinusitis: Background, History of the Procedure, Problem". eMedicine. 28 June 2016. Retrieved 25 November 2016.
2. ^ P. Karthikeyan, V. Nirmal Coumare (October–December 2010). "Incidence and presentation of fungal sinusitis in patient diagnosed with chronic rhinosinusitis". Indian Journal of Otolaryngology Head and Neck Surgery. 62 (4): 381–5. doi:10.1007/s12070-010-0062-0. PMC 3266098. PMID 22319697.CS1 maint: uses authors parameter (link)subscription needed
3. ^ a b c d e f "Granulomatous Diseases of the Head and Neck: Overview, Autoimmune Granulomatous Diseases, Granulomatous Diseases of Unknown Etiology". eMedicine. 2018-08-24. Retrieved 11 September 2016.
4. ^ Chakrabarti, Arunaloke; Denning, David W.; Ferguson, Berrylin J.; Ponikau, Jens; Buzina, Walter; Kita, Hirohito; Marple, Bradley; Panda, Naresh; Vlaminck, Stephan (2017-01-29). "Fungal Rhinosinusitis: A Categorization and Definitional Schema Addressing Current Controversies". The Laryngoscope. 119 (9): 1809–1818. doi:10.1002/lary.20520. ISSN 0023-852X. PMC 2741302. PMID 19544383.
5. ^ a b c d "Sinusitis. Medical professional reference for Sinusitis. | Patient". Patient. Retrieved 29 January 2017.
6. ^ Glass, Daniel; Amedee, Ronald G. (1 January 2011). "Allergic Fungal Rhinosinusitis: A Review". The Ochsner Journal. 11 (3): 271–275. ISSN 1524-5012. PMC 3179194. PMID 21960761.
7. ^ Soler, Zachary M.; Schlosser, Rodney J. (1 January 2012). "The role of fungi in diseases of the nose and sinuses". American Journal of Rhinology & Allergy. 26 (5): 351–358. doi:10.2500/ajra.2012.26.3807. ISSN 1945-8924. PMC 3904040. PMID 23168148.
8. ^ Hupp, James R.; Ferneini, Elie M. (2016). Head, Neck and Orofacial Infections: An Interdisciplinary Approach E-Book. Elsevier Health Sciences. p. 45. ISBN 9780323289467. Retrieved 4 March 2017.
9. ^ Karthikeyan, P.; Nirmal Coumare, V. (2017-01-29). "Incidence and Presentation of Fungal Sinusitis in Patient Diagnosed with Chronic Rhinosinusitis". Indian Journal of Otolaryngology and Head & Neck Surgery. 62 (4): 381–385. doi:10.1007/s12070-010-0062-0. ISSN 2231-3796. PMC 3266098. PMID 22319697.
## Further reading[edit]
* Thaler, Erica; Kennedy, David W. (2008). Rhinosinusitis: A Guide for Diagnosis and Management. Springer Science & Business Media. ISBN 9780387730622. Retrieved 22 February 2017.
* Aribandi, Manohar; McCoy, Victor A.; Bazan, Carlos (2007). "Imaging Features of Invasive and Noninvasive Fungal Sinusitis: A Review". RadioGraphics. 27 (5): 1283–1296. doi:10.1148/rg.275065189. PMID 17848691.
## External links[edit]
Classification
D
* ICD-10: J30.89
External resources
* eMedicine: Sinusitis/863062-overview Fungal Sinusitis/863062
Scholia has a topic profile for Fungal sinusitis.
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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
| Fungal sinusitis | c1142077 | 2,342 | wikipedia | https://en.wikipedia.org/wiki/Fungal_sinusitis | 2021-01-18T18:47:27 | {"umls": ["C1142077"], "icd-10": ["J32.9"], "wikidata": ["Q23808336"]} |
Most common form of cutaneous mastocytosis
Urticaria pigmentosa
Other namesGeneralized eruption of cutaneous mastocytosis (childhood type)
The back of a child with urticaria pigmentosa
SpecialtyMedical genetics
Urticaria pigmentosa (also known as generalized eruption of cutaneous mastocytosis (childhood type)[1]:616 ) is the most common form of cutaneous mastocytosis. It is a rare disease caused by excessive numbers of mast cells in the skin that produce hives or lesions on the skin when irritated.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Irritants
* 3 Diagnosis
* 4 Treatments
* 5 Epidemiology
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
## Signs and symptoms[edit]
Urticaria pigmentosa is characterized by excessive amounts of mast cells in the skin. Red or brown spots are often seen on the skin, typically around the chest, forehead, and back. These mast cells, when irritated (e.g. by rubbing the skin, heat exposure), produce too much histamine, triggering an allergic reaction that leads to hives localized to the area of irritation, sometimes referred to as Darier's sign. Severe itching usually follows, and scratching the area only serves to further symptoms. Symptoms can be mild (flushing and hives that require no treatment), moderate (diarrhea, tachycardia, nausea/vomiting, headache, and fainting), or life-threatening (vascular collapse requiring emergency treatment and hospitalization).[citation needed]
## Cause[edit]
The majority of urticaria pigmentosa cases are caused by a point mutation at amino acid 816 of the proto-oncogene c-kit.[2] c-kit is a transmembrane protein which, when bound to Mast Cell Growth Factor (MCGF), signals the cell to divide. Mutations in position 816 of c-kit can result in a constant division signal being sent to the mast cells, resulting in abnormal proliferation. Different mutations have been linked to different onset times of the disease. For example, the Asp816Phe and Asp816Val mutations (the aspartate normally at position 816 in the c-kit protein has been replaced with phenylalanine or valine respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively).[3][4] The c-kit gene is encoded on the q12 locus of chromosome 4.[5]
### Irritants[edit]
Several factors can worsen the symptoms of urticaria pigmentosa:[citation needed]
* Emotional stress
* Physical stimuli such as heat, friction, and excessive exercise
* Bacterial toxins
* Venom
* Eye drops containing dextran
* NSAIDs
* Alcohol
* Morphine
The classification of NSAIDs can be disputed. Aspirin, for example, causes the mast cells to degranulate, releasing histamines and causing symptoms to flare. However, daily intake of 81 mg aspirin may keep the mast cells degranulated. Thus, while symptoms may be worsened at first, they can get better as the mast cells are unable to recharge with histamine.[citation needed]
## Diagnosis[edit]
Histopathology of urticaria pigmentosa, showing plenty of spindle shaped cells with eosinophilic cytoplasm i.e. mast cells infiltrating the dermis and the appendiceal structures (black arrows). The basal cells show more pigmentation (blue arrows).[6]
The disease is most often diagnosed as an infant, when parents take their baby in for what appears to be bug bites. The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the baby's skin. If hives appear, it most likely signifies the presence of urticaria pigmentosa.[citation needed]
## Treatments[edit]
There are no permanent cures for urticaria pigmentosa. However, treatments are possible. Most treatments for mastocytosis can be used to treat urticaria pigmentosa. Many common anti-allergy medications are useful because they reduce the mast cell's ability to react to histamine.[7]
At least one clinical study suggested that nifedipine, a calcium channel blocker used to treat high blood pressure, may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid.[8] However, nifedipine has never been approved by the FDA for treatment of urticaria pigmentosa.
Another mast cell stabilizer Gastrocrom, a form of cromoglicic acid has also been used to reduce mast cell degranulation.[citation needed]
## Epidemiology[edit]
Urticaria pigmentosa is a rare disease, affecting fewer than 200,000 people in the United States.
## See also[edit]
* Urticaria
* Dermatographic urticaria
* Generalized eruption of cutaneous mastocytosis (adult type)
## 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. ^ Akin C (2006). "Molecular Diagnosis of Mast Cell Disorders : A Paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology". J Mol Diagn. 8 (4): 412–9. doi:10.2353/jmoldx.2006.060022. PMC 1867614. PMID 16931579.
3. ^ Yanagihori H, Oyama N, Nakamura K, Kaneko F (2005). "c-kit Mutations in Patients with Childhood-Onset Mastocytosis and Genotype-Phenotype Correlation". J Mol Diagn. 7 (2): 252–7. doi:10.1016/S1525-1578(10)60552-1. PMC 1867517. PMID 15858149.
4. ^ Sotlar K, Escribano L, Landt O, et al. (2003). "One-Step Detection of c-kit Point Mutations Using Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping and Hybridization Probes". Am. J. Pathol. 162 (3): 737–46. doi:10.1016/S0002-9440(10)63870-9. PMC 1868096. PMID 12598308.
5. ^ url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIT&keywords=C-kit
6. ^ Tamhankar, Parag M; Suvarna, Jyoti; Deshmukh, Chandrahas T (2009). "Cutaneous mastocytosis. Getting beneath the skin of the issue: a case report". Cases Journal. 2 (1): 69. doi:10.1186/1757-1626-2-69. ISSN 1757-1626. PMC 2651115. PMID 19154597.
7. ^ [1]
8. ^ Fairley JA, Pentland AP, Voorhees JJ (1984). "Urticaria pigmentosa responsive to nifedipine". J. Am. Acad. Dermatol. 11 (4 Pt 2): 740–3. doi:10.1016/S0190-9622(84)70233-7. PMID 6491000.
## Further reading[edit]
* Alto WA, Clarcq L (June 1999). "Cutaneous and systemic manifestations of mastocytosis". Am Fam Physician. 59 (11): 3047–54, 3059–60. PMID 10392589.
## External links[edit]
Classification
D
* ICD-10: Q82.2
* ICD-9-CM: 757.33
* MeSH: D014582
* DiseasesDB: 7864
External resources
* MedlinePlus: 001466
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
*[v]: View this template
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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
| Urticaria pigmentosa | c0042111 | 2,343 | wikipedia | https://en.wikipedia.org/wiki/Urticaria_pigmentosa | 2021-01-18T18:47:07 | {"gard": ["12093"], "mesh": ["D014582"], "umls": ["C0042111"], "icd-9": ["757.33"], "orphanet": ["79457"], "wikidata": ["Q3886247"]} |
A very rare genetic multisystemic disorder characterized by pituitary dysfunction, ataxia, peripheral neuropathy, spastic paraplegia, and chorioretinal dystrophy.
*[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
| Laurence-Moon syndrome | c0023138 | 2,344 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2377 | 2021-01-23T18:15:10 | {"gard": ["12635"], "mesh": ["D007849"], "omim": ["245800"], "umls": ["C0023138"], "icd-10": ["Q87.8"]} |
Intestinal pseudo-obstruction is a digestive disorder in which the intestinal walls are unable to contract normally (called hypomotility); the condition resembles a true obstruction, but no actual blockage exists. Signs and symptoms may include abdominal pain; vomiting; diarrhea; constipation; malabsorption of nutrients leading to weight loss and/or failure to thrive; and other symptoms. It may be classified as neuropathic (from lack of nerve function) or myopathic (from lack of muscle function), depending on the source of the abnormality. The condition is sometimes inherited (in an X-linked recessive or autosomal dominant manner) and may be caused by mutations in the FLNA gene; it may also be acquired after certain illnesses. The goal of treatment is to provide relief from symptoms and ensure that nutritional support is adequate.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Intestinal pseudo-obstruction | c1864996 | 2,345 | gard | https://rarediseases.info.nih.gov/diseases/6789/intestinal-pseudo-obstruction | 2021-01-18T17:59:45 | {"mesh": ["C566502"], "omim": ["609629"], "synonyms": ["Intestinal pseudoobstruction", "Hollow visceral myopathy"]} |
Tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS) is a condition characterized by recurrent episodes of fever. These fevers typically last about 3 weeks but can last from a few days to a few months. The frequency of the episodes varies greatly among affected individuals; fevers can occur anywhere between every 6 weeks to every few years. Some individuals can go many years without having a fever episode. Fever episodes usually occur spontaneously, but sometimes they can be brought on by a variety of triggers, such as minor injury, infection, stress, exercise, or hormonal changes.
During episodes of fever, people with TRAPS can have additional signs and symptoms. These include abdominal and muscle pain and a spreading skin rash, typically found on the limbs. Affected individuals may also experience puffiness or swelling in the skin around the eyes (periorbital edema); joint pain; and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat, or mucous membranes such as the moist lining of the mouth and digestive tract. Occasionally, people with TRAPS develop amyloidosis, an abnormal buildup of a protein called amyloid in the kidneys that can lead to kidney failure. It is estimated that 15 to 20 percent of people with TRAPS develop amyloidosis, typically in mid-adulthood.
The fever episodes characteristic of TRAPS can begin at any age, from infancy to late adulthood, but most people have their first episode in childhood.
## Frequency
TRAPS has an estimated prevalence of one per million individuals; it is the second most common inherited recurrent fever syndrome, following a similar condition called familial Mediterranean fever. More than 1,000 people worldwide have been diagnosed with TRAPS.
## Causes
TRAPS is caused by mutations in the TNFRSF1A gene. This gene provides instructions for making a protein called tumor necrosis factor receptor 1 (TNFR1). This protein is found within the membrane of cells, where it attaches (binds) to another protein called tumor necrosis factor (TNF). This binding sends signals that can trigger the cell either to initiate inflammation or to self-destruct. Signaling within the cell initiates a pathway that turns on a protein called nuclear factor kappa B that triggers inflammation and leads to the production of immune system proteins called cytokines. The self-destruction of the cell (apoptosis) is initiated when the TNFR1 protein, bound to the TNF protein, is brought into the cell and triggers a process known as the caspase cascade.
Most TNFRSF1A gene mutations that cause TRAPS result in a TNFR1 protein that is folded into an incorrect 3-dimensional shape. These misfolded proteins are trapped within the cell and are not able to get to the cell surface to interact with TNF. Inside the cell, these proteins clump together and are thought to trigger alternative pathways that initiate inflammation. The clumps of protein constantly activate these alternative inflammation pathways, leading to excess inflammation in people with TRAPS. Additionally, because only one copy of the TNFRSF1A gene has a mutation, some normal TNFR1 proteins are produced and can bind to the TNF protein, leading to additional inflammation. It is unclear if disruption of the apoptosis pathway plays a role in the signs and symptoms of TRAPS.
### Learn more about the gene associated with Tumor necrosis factor receptor-associated periodic syndrome
* TNFRSF1A
## 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. However, some people who inherit the altered gene never develop features of TRAPS. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with the mutated gene do not.
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
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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
| Tumor necrosis factor receptor-associated periodic syndrome | c1275126 | 2,346 | medlineplus | https://medlineplus.gov/genetics/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome/ | 2021-01-27T08:25:18 | {"gard": ["8457"], "mesh": ["C536657"], "omim": ["142680"], "synonyms": []} |
Hereditary angioedema (HAE) is a genetic disease characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and/or abdominal pain.
## Epidemiology
Prevalence has been estimated at 1/100,000.
## Clinical description
Onset may occur at any age but is most common during childhood or adolescence. Patients present with white, circumscribed nonpruritic edemas that remain for a period of 48 to 72 hours and recur with variable frequency. Edemas may involve the digestive tract resulting in a clinical picture similar to that seen in intestinal occlusion syndrome, sometimes associated with ascites and hypovolemic shock. Laryngeal edema can be life-threatening with a risk of death of 25% in the absence of appropriate treatment. Dental procedures are a triggering factor for laryngeal edema. Edemas of the face are a risk factor for laryngeal involvement.
## Etiology
Three types of HAE have been described. HAE types 1 and 2 are caused by anomalies in the SERPING1 gene (11q12-q13-1) encoding the C1 inhibitor (C1-INH): type 1 is caused by deletion or by expression of a truncated transcript leading to a quantitative defect in C1-INH; type 2 is caused by point mutations leading to a qualitative defect in C1-INH. Transmission is autosomal dominant and most cases involve heterozygotes. The edemas are triggered by increased permeability of the blood vessels in response to elevated levels of bradykinin as a result of the C1-INH deficiency. HAE type 3 predominantly involves females, with the use of estrogen-containing oral contraceptives and pregnancy being precipitating factors. HAE type 3 is not caused by C1-INH deficiency but is associated with an increase in kininogenase activity leading to elevated levels of bradykinin. Some cases are associated with coagulation factor 12 (Hageman factor; F12; 5q33-qter) gain-of-function mutations but other genetic anomalies remain to be identified.
## Diagnostic methods
Diagnosis of HAE types 1 and 2 relies on measurement of C4 concentrations and on quantitative and functional analysis of C1-INH. Diagnosis of HAE type 3 revolves around recognition of the clinical picture; C4 and C1-INH levels are normal. Analysis for mutations in the F12 gene may be proposed but are present in only 15% of patients.
## Differential diagnosis
The differential diagnosis should include acquired angioedema (see this term), intestinal occlusion syndrome and histamine-induced angioedema (of allergenic or nonallergenic origin) generally associated with urticaria. Screening of family members, including asymptomatic individuals, is recommended.
## Management and treatment
Corticosteroid treatments are not effective. In Europe, acute attacks should be treated with subcutaneous icatibant (a bradykinin receptor antagonist) or intravenous administration of C1-INH concentrate. Prophylactic treatment with tranexamic acid or danazol may be proposed for patients with frequent episodes.
## Prognosis
The vital prognosis is good for patients who have been diagnosed and have access to the proper treatment in case of an ear-nose-throat (ENT) edema. Significant morbidity may be associated with digestive involvement resulting in pain and patients becoming bedridden for at least three days following an episode.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Hereditary angioedema | c0019243 | 2,347 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91378 | 2021-01-23T19:04:33 | {"gard": ["5979"], "mesh": ["D054179"], "omim": ["106100", "610618"], "umls": ["C0019243"], "icd-10": ["D84.1"], "synonyms": ["Familial angioneurotic edema", "HAE", "Hereditary angioneurotic edema", "Hereditary bradykinine-induced angioedema", "Hereditary non histamine-induced angioedema"]} |
A number sign (#) is used with this entry because of evidence that Leber congenital amaurosis-19 (LCA19) is caused by homozygous mutation in the USP45 gene (618439) on chromosome 6q16. One such patient has been reported.
Description
Leber congenital amaurosis-19 (LCA19) is characterized by reduced vision in early childhood and severely reduced responses of both rods and cones on electroretinography (Yi et al., 2019).
For a general description and a discussion of genetic heterogeneity of LCA, see 204000.
Clinical Features
Yi et al. (2019) reported 2 unrelated Chinese children with Leber congenital amaurosis and mutations in the USP45 gene. One patient was a 9-year-old boy (family 1) who experienced nystagmus and poor vision from early childhood. Electroretinography showed severely reduced responses of both rods and cones. Fundus examination showed a pale optic disc, attenuated retinal arteries, and carpet-like degeneration in the mid-peripheral retina. The second patient was a 3-month-old girl (family 2) who exhibited inattention to light. Ophthalmologic examination confirmed no pursuit of light and showed sluggish pupillary light reflex, mildly pale temporal optic disc, and undetectable cone or rod responses on electroretinography. The parents in both families had normal vision and fundus appearance.
Molecular Genetics
Yi et al. (2019) analyzed exome data from 269 Chinese probands with LCA who did not have a mutation in known eye disease-associated genes and identified 2 unrelated patients who were homozygous for a missense mutation affecting splicing (R312Q; 618439.0001) and a nonsense mutation (K546X; 618439.0002), respectively, in the USP45 gene. Their unaffected parents were heterozygous for the variants, which were not found in 3,011 in-house probands with other hereditary eye diseases. Yi et al. (2019) found that both variants were present at very low frequency in the ExAC database, but Hamosh (2019) found that the K546X mutation was found in 137 of 282,556 alleles and in 2 homozygotes in the gnomAD database (July 24, 2019).
INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Reduced vision \- Pale optic disc \- Attenuated retinal arteries \- Retinal degeneration, carpet-like, in midperiphery \- Reduced cone and rod responses, severe, seen on electroretinography MISCELLANEOUS \- Onset of symptoms in early childhood \- Based on report of 1 patient (last curated July 2019) MOLECULAR BASIS \- Caused by mutation in the ubiquitin-specific protease-45 gene (USP45, 618439.0001 ) ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| LEBER CONGENITAL AMAUROSIS 19 | None | 2,348 | omim | https://www.omim.org/entry/618513 | 2019-09-22T15:41:36 | {"omim": ["618513"]} |
Stimmler et al. (1970) described 2 sisters born in 1963 and 1964 with microcephaly at birth, low birth weight, severe mental retardation and dwarfism, small teeth, and diabetes mellitus. Excessive quantities of alanine were found in the urine. Alanine, pyruvate, and lactate were elevated in the blood. Pyruvate was thought to be a source of the alanine. The authors contrasted the findings with those in the condition described by Haworth et al. (1967) and in Leigh subacute necrotizing encephalopathy with lactic acidosis (Worsley et al., 1965). The main differences were elevated plasma chloride and lack of hyperalaninemia in the other two conditions.
Head \- Microcephaly Inheritance \- Autosomal recessive Endocrine \- Diabetes mellitus Lab \- Alaninuria \- Lacticacidosis Growth \- Dwarfism Teeth \- Enamel hypoplasia ▲ 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
| ALANINURIA WITH MICROCEPHALY, DWARFISM, ENAMEL HYPOPLASIA, AND DIABETES MELLITUS | c1859965 | 2,349 | omim | https://www.omim.org/entry/202900 | 2019-09-22T16:31:22 | {"mesh": ["C565968"], "omim": ["202900"], "orphanet": ["3199"], "synonyms": ["Alternative titles", "STIMMLER SYNDROME"]} |
Lacquer dermatitis
SpecialtyDermatology
Lacquer dermatitis (also known as "Lacquer sensitivity") is a cutaneous condition characterized by a contact dermatitis to various lacquers.[1]
## See also[edit]
* Toxicodendron dermatitis
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
This dermatology 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
| Lacquer dermatitis | None | 2,350 | wikipedia | https://en.wikipedia.org/wiki/Lacquer_dermatitis | 2021-01-18T18:57:12 | {"wikidata": ["Q6468835"]} |
A number sign (#) is used with this entry because Smith-McCort dysplasia-1 (SMC1) is caused by homozygous or compound heterozygous mutation in the DYM gene (607461) on chromosome 18q21.
Mutations in the same gene cause Dyggve-Melchior-Clausen disease (DMC; 223800), which is radiologically identical but has the additional feature of mental retardation.
Description
Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest, features identical to those of Dyggve-Melchior-Clausen disease. Spinal cord compression due to atlantoaxial instability occurs in both SMC and DMC (Spranger et al., 1976; Nakamura et al., 1997).
### Genetic Heterogeneity of Smith-McCort Dysplasia
Smith-McCort dysplasia-2 (SMC2; 615222) is caused by mutation in the RAB33B gene (605950) on chromosome 4q31.
Clinical Features
Nakamura et al. (1997) examined iliac crest biopsies from 2 patients with Smith-McCort dysplasia. The lace-like appearance of the iliac crests, which is a characteristic radiologic sign, was caused by bone tissue deposited in a wavy pattern at the osteochondral junction. The growth plate showed abnormal enchondral ossification with no columnarization of chondrocytes. Electron microscopy demonstrated chondrocytes with dilated cisternae of rough endoplasmic reticulum (RER) containing fine granular or amorphous material similar to what had been reported in cases of DMC syndrome. Thus, Nakamura et al. (1997) concluded that Smith-McCort dysplasia has pathologic changes in common with DMC disease as an RER storage disorder, even though the mental condition is different.
Mapping
In a consanguineous family from Guam affected by Smith-McCort dysplasia, Ehtesham et al. (2002) performed a genomewide scan and found evidence of linkage to loci on chromosome 18q12. Analysis of a second, smaller family was also consistent with linkage to this region, producing a maximum combined 2-point lod score of 3.04 at a recombination fraction of zero for marker D18S450. A 10.7-cM region containing the disease locus was defined by recombination events in 2 affected individuals in the larger family. Furthermore, all affected children in the larger family were homozygous for a subset of marker loci within this region, defining a 1.5-cM interval likely to contain the mutated gene. Analysis of 3 small, unrelated families with DMC syndrome provided evidence of linkage to the same region, a result consistent with the hypothesis that the 2 disorders are allelic.
Molecular Genetics
In patients with SMC, Cohn et al. (2003) identified mutations in the DYM gene (607461.0005-607461.0006).
In an affected 6-year-old girl, offspring of consanguineous parents from the Portuguese Madeira Island, Santos et al. (2009) identified homozygosity for a mutation in the DYM gene (607461.0010).
Nomenclature
Spranger et al. (1976) suggested the designation Smith-McCort dwarfism for this disorder.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, disproportionate (short trunk) HEAD & NECK Head \- Dolichocephaly \- Microcephaly CHEST External Features \- Short barrel-shaped chest Ribs Sternum Clavicles & Scapulae \- Sternal protrusion \- Short scapulae SKELETAL Skull \- Small calvarium \- Deformed sella turcica \- Hypoplastic facial bones Spine \- Atlantoaxial instability \- Odontoid hypoplasia \- Platyspondyly \- Scoliosis \- Kyphosis \- Anterior beaking of vertebral bodies Pelvis \- Lacy iliac crest \- Hypoplastic acetabulae \- Short ischia \- Wide symphysis pubis \- Thick femoral neck \- Delayed femoral head ossification \- Multicentric femoral head ossification Limbs \- Irregular metaphyses \- Irregular epiphyses \- Genu valgum \- Genu varum Hands \- Short metacarpals \- Short phalanges NEUROLOGIC Central Nervous System \- Normal intelligence MISCELLANEOUS \- Allelic to Dyggve-Melchior-Clausen disease ( 223800 ) \- Waddling gait MOLECULAR BASIS \- Caused by mutations in the FLJ90140 gene (FLJ90130, 607461.0005 ) ▲ 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
| SMITH-MCCORT DYSPLASIA 1 | c1846431 | 2,351 | omim | https://www.omim.org/entry/607326 | 2019-09-22T16:09:25 | {"doid": ["0060247"], "mesh": ["C564589"], "omim": ["607326"], "orphanet": ["178355"], "synonyms": ["Alternative titles", "SMC"]} |
Buschke–Ollendorff sign
Other namesDermatofibrosis lenticularis disseminata[1]
Buschke–Ollendorff syndrome has an autosomal dominant pattern of inheritance.
SymptomsOsteopoikilosis, bone pain[2]
CausesMutations in the LEMD3 gene.[2]
Diagnostic methodX-ray, ultrasound[3]
TreatmentSurgery for hearing loss(or complications)[4]
Buschke–Ollendorff syndrome (BOS)is a rare genetic disorder associated with LEMD3. It is believed to be inherited in an autosomal dominant manner.[5] It is named for Abraham Buschke and Helene Ollendorff Curth,[6] who described it in a 45-year-old woman. Its frequency is almost 1 case per every 20,000 people, and it is equally found in both males and females.[4]
## Contents
* 1 Signs and symptoms
* 2 Pathogenesis
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 Further reading
* 8 External links
## Signs and symptoms[edit]
Osteopoikilosis
The signs and symptoms of this condition are consistent with the following (possible complications include aortic stenosis and hearing loss[2][4]):
* Osteopoikilosis
* Bone pain
* Connective tissue nevi
* Metaphysis abnormality
## Pathogenesis[edit]
Buschke–Ollendorff syndrome is caused by one important factor: mutations in the LEMD3 gene (12q14), located on chromosome 12.[citation needed]
Among the important aspects of Buschke–Ollendorff syndrome condition, genetically speaking are:[7][8][9]
Bone Cells
* LEMD3 (protein) referred also as MAN1, is an important protein in inner nuclear membrane.
* LEMD3 gene gives instructions for producing protein that controls signaling for transforming growth factor-beta.
* LEMD3 gene helps in the bone morphogenic protein pathway
* Both of the above pathways help grow new bone cells
* BMP and TGF-β pathways controls SMADs proteins, which then bind to DNA
* LEMD3 once mutated, causes a reduction of the protein, which in turn causes excess of the above two pathways.
## Diagnosis[edit]
Microscope with stained slide (histological specimen)
Histopathology of BOS.[10]
The diagnosis of this condition can be ascertained via several techniques one such method is genetic testing, as well as:[2][3]
* X-ray
* Ultrasound
* Histological test
### Differential diagnosis[edit]
The differential diagnosis for an individual believed to have Buschke–Ollendorff syndrome is the following:[3]
* Melorheostosis
* Sclerotic bone metastases.
## Treatment[edit]
In terms of the treatment of Buschke–Ollendorff syndrome, should the complication of aortic stenosis occur then surgery may be required. [4]
Treatment for hearing loss may also require surgical intervention.[4]
## See also[edit]
* Osteopoikilosis
* List of cutaneous conditions
* Melorheostosis
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ a b c d "Buschke Ollendorff syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 29 December 2017.
3. ^ a b c RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Buschke Ollendorff syndrome". www.orpha.net. Retrieved 29 December 2017.
4. ^ a b c d e Lukasz Matusiak (2 July 2008), Dermatofibrosis Lenticularis (Buschke–Ollendorf Syndrome), eMedicine, retrieved 2009-09-05
5. ^ Online Mendelian Inheritance in Man (OMIM): 166700
6. ^ A. Buschke, H. Ollendorff-Curth. Ein Fall von Dermatofibrosis lenticularis disseminata und Osteopathia condensans disseminata. Dermatologische Wochenschrift, Hamburg, 1928, 86: 257–262.
7. ^ Reference, Genetics Home. "Buschke-Ollendorff syndrome". Genetics Home Reference. Retrieved 2018-05-13.
8. ^ Worman, Howard J.; Fong, Loren G.; Muchir, Antoine; Young, Stephen G. (July 2009). "Laminopathies and the long strange trip from basic cell biology to therapy". The Journal of Clinical Investigation. 119 (7): 1825–1836. doi:10.1172/JCI37679. ISSN 1558-8238. PMC 2701866. PMID 19587457. Retrieved 13 May 2018.
9. ^ Reference, Genetics Home. "LEMD3 gene". Genetics Home Reference. Retrieved 2018-05-13.
10. ^ Hosen, Mohammad J.; Lamoen, Anouck; De Paepe, Anne; Vanakker, Olivier M. (2012). "Histopathology of Pseudoxanthoma Elasticum and Related Disorders: Histological Hallmarks and Diagnostic Clues". Scientifica. 2012: 1–15. doi:10.6064/2012/598262. ISSN 2090-908X. PMC 3820553. PMID 24278718.
-Creative Commons Attribution 3.0 Unported license
## Further reading[edit]
* Pope, V.; Dupuis, L.; Kannu, P.; Mendoza-Londono, R.; Sajic, D.; So, J.; Yoon, G.; Lara-Corrales, I. (2016). "Buschke-Ollendorff syndrome: a novel case series and systematic review". The British Journal of Dermatology. 174 (4): 723–729. doi:10.1111/bjd.14366. ISSN 1365-2133. PMID 26708699. S2CID 24066368.
* Helander, Martti Kormano, Ilmari Lindgren; with the collaboration of Inkeri; Lindgren, Ilmari (1999). Radiological findings in skin diseases and related conditions. Stuttgart: Thieme. ISBN 9783131161215. Retrieved 3 February 2018.
## External links[edit]
* Media related to Buschke–Ollendorff syndrome at Wikimedia Commons
* PubMed
Classification
D
* ICD-10: Q78.8
* OMIM: 166700
* MeSH: C537415
* DiseasesDB: 30071
External resources
* Orphanet: 1306
Scholia has a topic profile for Buschke–Ollendorff syndrome.
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Cytoskeletal defects
Microfilaments
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Actin
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IF
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3
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4
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5
* Laminopathy: LMNA
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* LMNB
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Kinesin
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* plakophilin: Skin fragility syndrome
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* centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II)
Related topics: Cytoskeletal 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
| Buschke–Ollendorff syndrome | c0265514 | 2,352 | wikipedia | https://en.wikipedia.org/wiki/Buschke%E2%80%93Ollendorff_syndrome | 2021-01-18T18:37:30 | {"gard": ["1044"], "mesh": ["C537415"], "orphanet": ["1306"], "wikidata": ["Q5001316"]} |
A rare, syndromic intellectual disability characterized by hypotonia, developmetal delay, absent or severly delayed speech development, intellectual disability, obstructive sleep apnea, mild dysmorphic facial features and behavioral abnormalities. Epilepsy, ataxia and nystagmus have also been reported.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome | c4014419 | 2,353 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=412069 | 2021-01-23T18:04:51 | {"omim": ["615829"], "icd-10": ["Q87.8"], "synonyms": ["Xia-Gibbs syndrome"]} |
For a clinical description of atopic dermatitis (ATOD) and an overview of linkage studies, see ATOD1 (603165).
Mapping
Using a nonparametric affected relative-pair method in 109 atopic dermatitis pedigrees, Bradley et al. (2002) conducted a genomewide linkage analysis with 367 microsatellite markers and found linkage to chromosome 3p24-p22 (D3S1768, lod = 2.18, p less than 0.001). The authors noted that polymorphic markers at 3p24-p22 have also been linked to asthma (see 600807) in various populations, suggesting that more than 1 phenotype of atopic hypersensitivity may be influenced by genes in this region.
In a linkage study involving a total of 346 children with atopic dermatitis and 306 parents from 153 Danish nuclear families, Christensen et al. (2009) obtained a maximum MOD score of 4.6 at chromosome 3p24 for the ATOD phenotype.
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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
| DERMATITIS, ATOPIC, 9 | c3150764 | 2,354 | omim | https://www.omim.org/entry/613519 | 2019-09-22T15:58:29 | {"omim": ["613519"]} |
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Find sources: "Pascual-Castroviejo syndrome type 1" – news · newspapers · books · scholar · JSTOR (April 2018) (Learn how and when to remove this template message)
Pascual-Castroviejo syndrome type 1
Other namesCerebrofaciothoracic dysplasia
Autosomal recessive pattern is the inheritance manner of this condition.
CausesMutations in the TMCO1 gene
Pascual-Castroviejo syndrome type 1 is a rare autosomal recessive condition characterized by facial dysmorphism, cognitive impairment and skeletal anomalies.
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 3.1 Differential diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 History
* 8 References
* 9 External links
## Signs and symptoms[edit]
These can be divided into four areas[citation needed]
* Facial features
* Brachycephaly
* Low hairline
* Narrow forehead
* Bushy eyebrows
* Synophrys
* Hypertelorism
* Ptosis
* Broad nose
* Wide philtrum
* Triangular shaped mouth
* Maxillary hypoplasia
* Cleft lip and palate
* Small conical teeth
* Short neck
* Skeletal abnormalities
* Abnormalities of the upper thoracic vertebrae and ribs
* Hypermobility
* Talipes (clubfoot)
* Central nervous system
* Hypoplasia of the corpus callosum and cerebellar vermis
* Cognitive impairment
* Chiari I malformation
* Optic nerve colobomas
* Grey matter hypodensity
* Other
* Hypothyroidism
## Genetics[edit]
This disease is caused by mutations in the transmembrane and coiled-coil domain-containing protein 1 (TMCO1) on the long arm of chromosome 1.[citation needed]
## Diagnosis[edit]
The diagnosis may be provisionally made on clinical grounds. Further diagnostic tests include serum and urine analysis for lactic acid, a chest X ray (or cardiac CT or MRI) and echocardiography. Biopsies from cardiac and skeletal muscle will show the presence of lipid and glycogen. Testing for mitochondrial abnormalities including adenosine nucleotide transporter deficiency and decreases in the respiratory chain complexes I and IV can also be done.
### Differential diagnosis[edit]
This condition forms part of the spectrum of TMCO1 defects. There may be some overlap in features.
## Treatment[edit]
There is no known treatment for this condition. Surgery may be helpful in treating the cleft lip and palate.
## Prognosis[edit]
All cases to date have been reported in children. Long term prognosis is not known.
## Epidemiology[edit]
Pascual-Castroviejo syndrome type 1 is rare. About 20 cases have been reported worldwide.
## History[edit]
This condition was first described in 1975.[1]
## References[edit]
1. ^ Pascual-Castroviejo I, Santolaya JM, Martin VL, Rodriguez-Costa T, Tendero A and Mulas F (1975) Cerebro-facio-thoracic dysplasia: Report of three cases. Dev Med Child Neurol 17:343–351
## External links[edit]
Classification
D
* OMIM: 213980
* MeSH: C565862
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Pascual-Castroviejo syndrome type 1 | c1859252 | 2,355 | wikipedia | https://en.wikipedia.org/wiki/Pascual-Castroviejo_syndrome_type_1 | 2021-01-18T18:32:45 | {"gard": ["1210"], "mesh": ["C565862"], "umls": ["C1859252"], "orphanet": ["1394"], "wikidata": ["Q55629168"]} |
Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCADN) is a nervous system disorder with signs and symptoms that usually begin in mid-adulthood and gradually get worse.
People with ADCADN have difficulty coordinating movements (ataxia) and mild to moderate hearing loss caused by abnormalities of the inner ear (sensorineural deafness). Most have excessive daytime sleepiness (narcolepsy). Narcolepsy is typically accompanied by cataplexy, which is a sudden brief loss of muscle tone in response to strong emotion (such as excitement, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. These characteristic signs and symptoms of ADCADN typically begin in a person's thirties.
Eventually, people with ADCADN also experience a decline of intellectual function (dementia). The cognitive problems often begin with impairment of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Other features that can occur as the condition worsens include degeneration of the nerves that carry information from the eyes to the brain (optic atrophy); clouding of the lenses of the eyes (cataracts); numbness, tingling, or pain in the arms and legs (sensory neuropathy); puffiness or swelling (lymphedema) of the limbs; an inability to control the bowels or the flow of urine (incontinence); depression; uncontrollable crying or laughing (pseudobulbar signs); or a distorted view of reality (psychosis). Affected individuals usually survive into their forties or fifties.
## Frequency
The prevalence of ADCADN is unknown. At least 24 affected individuals have been described in the medical literature.
## Causes
ADCADN is caused by mutations in the DNMT1 gene, which provides instructions for making an enzyme called DNA methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines.
DNA methyltransferase 1 is active in the adult nervous system. Although its specific role in the nervous system is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to move (migrate) where needed and connect with each other, and neuron survival.
DNMT1 gene mutations that cause ADCADN affect a region of the DNA methyltransferase 1 enzyme that helps target the methylation process to the correct segments of DNA. As a result of these mutations, methylation is abnormal, which affects the expression of multiple genes. Maintenance of the neurons that make up the nervous system is disrupted, leading to the signs and symptoms of ADCADN.
### Learn more about the gene associated with Autosomal dominant cerebellar ataxia, deafness, and narcolepsy
* DNMT1
## 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
| Autosomal dominant cerebellar ataxia, deafness, and narcolepsy | c3807295 | 2,356 | medlineplus | https://medlineplus.gov/genetics/condition/autosomal-dominant-cerebellar-ataxia-deafness-and-narcolepsy/ | 2021-01-27T08:24:53 | {"gard": ["12372"], "omim": ["604121"], "synonyms": []} |
ACAD9 deficiency is a condition that varies in severity and can cause muscle weakness (myopathy), heart problems, and intellectual disability. Nearly all affected individuals have a buildup of a chemical called lactic acid in the body (lactic acidosis). Additional signs and symptoms that affect other body systems occur in rare cases.
Mildly affected individuals with ACAD9 deficiency usually experience nausea and extreme fatigue in response to physical activity (exercise intolerance). People with ACAD9 deficiency who are moderately affected have low muscle tone (hypotonia) and weakness in the muscles used for movement (skeletal muscles). Severely affected individuals have brain dysfunction combined with myopathy (encephalomyopathy); these individuals usually also have an enlarged and weakened heart muscle (hypertrophic cardiomyopathy), which is typically fatal in infancy or childhood.
Individuals with ACAD9 deficiency who survive past early childhood often have intellectual disability and may develop seizures. Rare signs and symptoms of ACAD9 deficiency include movement disorders and problems with liver and kidney function.
Some individuals with ACAD9 deficiency have had improvement in muscle strength and a reduction in lactic acid levels with treatment.
## Frequency
The prevalence of ACAD9 deficiency is unknown. At least 25 people with this condition have been described in the scientific literature.
## Causes
ACAD9 deficiency is caused by mutations in the ACAD9 gene. This gene provides instructions for making an enzyme that is critical in helping assemble a group of proteins known as complex I. Complex I is found in mitochondria, which are the energy-producing structures inside cells. Complex I is one of several complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.
The ACAD9 enzyme also plays a role in fatty acid oxidation, a multistep process that occurs within mitochondria to break down (metabolize) fats and convert them into energy. The ACAD9 enzyme helps metabolize a certain group of fats called long-chain fatty acids. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues.
Some ACAD9 gene mutations disrupt complex I assembly as well as long-chain fatty acid oxidation, while others affect only complex I assembly. The mutations that affect both of the enzyme's functions tend to be associated with the most severe signs and symptoms of ACAD9 deficiency, such as encephalomyopathy and hypertrophic cardiomyopathy. Although the exact mechanism is unclear, it is likely that cells that are less able to produce energy die off, particularly cells in the brain, skeletal muscle, and other tissues and organs that require a lot of energy. The loss of cells in these tissues is thought to lead to the signs and symptoms of ACAD9 deficiency.
### Learn more about the gene associated with ACAD9 deficiency
* ACAD9
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| ACAD9 deficiency | c1970173 | 2,357 | medlineplus | https://medlineplus.gov/genetics/condition/acad9-deficiency/ | 2021-01-27T08:25:28 | {"gard": ["3908"], "mesh": ["C567006"], "omim": ["611126"], "synonyms": []} |
A rare systemic or rheumatologic disease characterized by peripheral osteolysis (especially carpal and tarsal bones), interphalangeal joint erosions, subcutaneous fibrocollagenous nodules, facial dysmorphism, and a wide range of associated manifestations.
## Epidemiology
Multicentric osteolysis-nodulosis-arthropathy (MONA) spectrum prevalence and incidence of MONA are not known. Fewer than 50 cases have been reported worldwide. Cases have been reported from Saudi Arabia, Italy, Turkey, Algeria, Morocco, the United States, and Korea.
## Clinical description
Onset is usually at preschool age (1-5 years) and the course of the disease is variable. Manifestations of the disorder include multiple peripheral osteolysis beginning at the carpal, tarsal, metacarpal/metatarsal-phalangeal and interphalangeal joints with subsequent generalization. The joint erosions lead to small hands and feet, arthropathy causing decreased range of motion, and progressive joint contractures. Some patients have been reported to have wide metacarpals and metatarsals, generalized osteoporosis of vertebrae, short stature, coarse face or facial dysmorphism (frontal bossing and hypertelorism), gum hypertrophy, corneal opacities, hyperpigmentation, hypertrichosis, and subcutaneous fibrocollagenous nodules. Associated cardiac malformations have been reported and included transposition of the great arteries, mitral valve prolapse, bicuspid aortic valve, and atrial and ventricular septal defects. Intrafamilial variability of manifestations is also found. Due to overlapping clinical features and the involvement of mutations in MMP2gene, Torg-Winchester syndrome and nodulosis-arthropathy-osteolysis (NAO) syndromes, that were originally reported separately, are now presumed to belong to the clinical spectrum of MONA (with other nomenclatures still being is use).
## Etiology
MONA spectrum disorders are caused by mutations in the MMP2 gene (16q13-q21) or MMP14 gene (14q11-q12). The pathogenesis of the disorder remains unclear.
## Diagnostic methods
The diagnosis is based on the clinical manifestations of the disease and can be confirmed by molecular genetic testing.
## Differential diagnosis
The main differential diagnoses are juvenile idiopathic arthritis and multicentric carpotarsal osteolysis.
## Genetic counseling
MONA spectrum disorders follow an autosomal recessive pattern on inheritance. Many cases are reported in children from consanguineous unions. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 25% risk of passing the mutation to offspring.
## Management and treatment
There is no specific treatment for MONA spectrum. Management is primarily symptomatic. Some patients initially respond to non-steroidal anti-inflammatory drugs (NSAIDs).
## Prognosis
The progressive joint destruction leads to significant disability; many patients are wheelchair bound. However, life expectancy does not appear to be significantly affected.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Multicentric osteolysis-nodulosis-arthropathy spectrum | c1850155 | 2,358 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=371428 | 2021-01-23T18:29:49 | {"mesh": ["C536051"], "omim": ["259600", "277950"], "icd-10": ["M89.5"], "synonyms": ["MONA spectrum", "NAO syndrome", "Nodulosis-arthropathy-osteolysis syndrome", "Torg-Winchester syndrome"]} |
17q12 duplication is a chromosomal change in which a small piece of chromosome 17 is copied (duplicated) abnormally in each cell. The duplication occurs on the long (q) arm of the chromosome at a position designated q12.
Signs and symptoms related to 17q12 duplications vary significantly, even among members of the same family. Some individuals with the duplication have no apparent signs or symptoms, or the features are very mild. Other individuals can have intellectual disability, delayed development, and a wide range of physical abnormalities.
Intellectual and learning ability in people with 17q12 duplications ranges from normal to severely impaired. Many affected individuals have delayed development, particularly involving speech and language skills and gross motor skills such sitting, standing, and walking. Seizures are also common. Behavioral and psychiatric conditions that have been reported in people with 17q12 duplications include autism spectrum disorder (which affects social interaction and communication), schizophrenia, aggression, and self-injury. About half of affected individuals have an unusually small head (microcephaly).
Less commonly, 17q12 duplications have been associated with abnormalities of the eyes, heart, kidneys, and brain. Some individuals with this chromosomal change have subtle differences in facial features, although these are not consistent.
## Frequency
17q12 duplications appear to be uncommon. Several dozen people with this chromosomal change have been described in the medical literature.
## Causes
Most people with 17q12 duplications have an extra copy of about 1.4 million DNA building blocks (base pairs), also written as 1.4 megabases (Mb), at position q12 on chromosome 17. This duplication affects one of the two copies of chromosome 17 in each cell.
The duplicated segment is surrounded by short, repeated sequences of DNA that make the segment prone to rearrangement during cell division. The rearrangement can lead to extra or missing copies of DNA at 17q12. (A missing copy of this segment causes a related chromosomal condition called 17q12 deletion syndrome.)
The segment of 17q12 that is most commonly duplicated includes at least 15 genes. It is unclear which of these genes, when present in more than one copy, contribute to intellectual disability, delayed development, and the other signs and symptoms described above. Because some people with a 17q12 duplication have no obvious intellectual or physical problems, researchers suspect that additional genetic factors may influence whether a person has signs and symptoms related to the chromosomal change.
### Learn more about the chromosome associated with 17q12 duplication
* chromosome 17
## Inheritance Pattern
17q12 duplications have an autosomal dominant pattern of inheritance, which means one copy of the duplication in each cell is sufficient to cause the signs and symptoms.
Most 17q12 duplications are inherited from a parent. In these cases, the parent most often has only mild signs and symptoms or no related features at all. Less commonly, 17q12 duplications represent a new (de novo) chromosomal change and occur in people with no history of the duplication 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
| 17q12 duplication | c3281137 | 2,359 | medlineplus | https://medlineplus.gov/genetics/condition/17q12-duplication/ | 2021-01-27T08:25:41 | {"omim": ["614526"], "synonyms": []} |
Injury caused by video games
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (August 2018) (Learn how and when to remove this template message)
Nintendo thumb, also known as gamer's grip, Nintendonitis and similar names, is a form of repetitive strain injury (RSI) caused by playing video games. The symptoms are the blistering, paraesthesia, and swelling of the thumbs, mainly through use of the D-pad, though any finger can be affected. This can lead to stress on tendons, nerves, and ligaments in the hands, and further onto lateral epicondylitis ("tennis elbow"), tendinitis, bursitis, and carpal tunnel syndrome (CTS).
Some of the symptoms are described under De Quervain syndrome.
Originally known in a video gaming context as "leather thumb", this condition was known to occur frequently among users of second-generation game consoles such as the Intellivision or the Atari 2600 in the late 1970s and early 1980s. The condition was first highlighted when the Nintendo games consoles were released, leading to reported cases of RSI, primarily in children (being one of the primary audiences of early-generation video games). Later, the controllers for the Sony PlayStation and PlayStation 2 were noted as causing the condition. However, due to the shape, size, and extended use of game controllers, it can occur in users of any gamepad or joystick. Similar problems have also been observed with the use of mobile phones and text messaging in particular (see Blackberry thumb).
## See also[edit]
* Video game-related health problems
* Blackberry thumb
* Tennis elbow
* Cello scrotum
* Golfer's elbow
* Jogger's nipple
* Surfer's ear
* Wiiitis
## References[edit]
* Brasington, Richard. "Nintendinitis" at New England Journal of Medicine, 17 May 1990. Retrieved 3 Oct 2014.
* Thompson, Dennis. "Video Game Victims" at Forbes, 6 May 2005. Retrieved 26 June 2005.
* "Girl probes 'PlayStation thumb'" at BBC News, 23 June 2005. Retrieved 26 June 2005.
* Moncur, Laura Blackberry thumb?, 14 November 2006. Retrieved 8 March 2014
## External links[edit]
* "Computer games pose injury risk" at BBC News, 23 December 1999.
* "'Nintendo Thumb' Points to RSI" at Wired News, 3 December 1998.
* "Computer games cripple kiddies" at The Register, 12 December 2000.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Nintendo thumb | None | 2,360 | wikipedia | https://en.wikipedia.org/wiki/Nintendo_thumb | 2021-01-18T19:01:56 | {"wikidata": ["Q7039177"]} |
Alagille syndrome is a genetic syndrome that can affect the liver and other parts of the body. The liver problems result from having fewer small bile ducts than normal in the liver. This leads to bile building-up inside the liver, which in turn causes liver scarring and damage. Signs and symptoms of Alagille syndrome are generally noticed in infancy or early childhood. Type of symptoms and severity varies greatly, even among people in the same family, so that in some cases the symptoms are severe, and in others, very mild. The liver problems may be the first symptoms of the syndrome, and may include yellow color of the skin and whites of the eyes (jaundice); itchy skin; bumps on the skin caused by deposits of cholesterol and fats (xanthomas); pale, loose bowel movements; and poor growth. Alagille syndrome can also affect other parts of the body including the heart, brain, kidneys, blood vessels, eyes, face, and skeleton. People with Alagille syndrome may have distinctive facial features too, including a broad, prominent forehead, deep-set eyes, and a small, pointed chin.
Alagille syndrome is caused by changes or mutations in the JAG1 and NOTCH2 genes. Inheritance is autosomal dominant. However, in about half of cases the mutation occurs as a new change ("de novo") without being inherited from either parents. While there is no known cure for Alagille syndrome, there are treatments that can help control symptoms. Possible treatments may include medication that increases the flow of bile and careful management of diet to minimize nutrition and vitamin related problems. In severe cases, a liver transplant may be necessary.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Alagille syndrome | c0085280 | 2,361 | gard | https://rarediseases.info.nih.gov/diseases/804/alagille-syndrome | 2021-01-18T18:02:13 | {"mesh": ["D016738"], "omim": ["118450"], "orphanet": ["52"], "synonyms": ["Hepatic ductular hypoplasia", "Watson Alagille syndrome", "Alagille-Watson syndrome", "Cholestasis with peripheral pulmonary stenosis", "Arteriohepatic dysplasia", "Paucity of interlobular bile ducts", "Cardiovertebral syndrome", "Watson-Miller syndrome", "Hepatofacioneurocardiovertebral syndrome"]} |
A rare soft tissue tumor characterized by a solitary mass-forming fibrous proliferation that usually occurs in the subcutaneous tissue, composed of uniform fibroblastic/myofibroblastic cells displaying a loose growth pattern. Upper extremities, trunk, and head and neck are most frequently affected. The lesion typically grows rapidly and almost always measures less than five centimeters in diameter. Macroscopically, it may appear circumscribed or infiltrative but is not encapsulated. Recurrence after excision is very rare, and metastasis does not 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
| Nodular fasciitis | c0410005 | 2,362 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=477742 | 2021-01-23T17:52:28 | {"synonyms": ["Pseudosarcomatous fasciitis", "Pseudosarcomatous fibromatosis"]} |
Binswanger's disease
Other namesSubcortical arteriosclerotic encephalopathy
SpecialtyNeurology
Binswanger's disease, also known as subcortical leukoencephalopathy and subcortical arteriosclerotic encephalopathy (SAE),[1] is a form of small vessel vascular dementia caused by damage to the white brain matter.[2] White matter atrophy can be caused by many circumstances including chronic hypertension as well as old age.[3] This disease is characterized by loss of memory and intellectual function and by changes in mood. These changes encompass what are known as executive functions of the brain.[4] It usually presents between 54 and 66 years of age, and the first symptoms are usually mental deterioration or stroke.[5]
It was described by Otto Binswanger in 1894, and[6] Alois Alzheimer first used the phrase "Binswanger's disease" in 1902.[7] However, Olszewski is credited with much of the modern-day investigation of this disease which began in 1962.[5][8]
## Contents
* 1 Signs and symptoms
* 1.1 Neurological presentation
* 1.2 Psychiatric presentation
* 2 Diagnosis
* 2.1 Imaging
* 3 Management
* 4 History
* 5 References
* 6 External links
## Signs and symptoms[edit]
Symptoms include mental deterioration, language disorder, transient ischemic attack, muscle ataxia, and impaired movements including change of walk, slowness of movements, and change in posture. These symptoms usually coincide with multiple falls, epilepsy, fainting, and uncontrollable bladder.[5] Because Binswanger's disease affects flow processing speed and causes impaired concentration, the ability to do everyday tasks such as managing finances, preparing a meal and driving may become very difficult.[3]
### Neurological presentation[edit]
Binswanger's disease is a type of subcortical vascular dementia caused by white matter atrophy to the brain. However, white matter atrophy alone is not sufficient for this disease; evidence of subcortical dementia is also necessary.[9]
The histologic findings are diffuse, irregular loss of axons and myelin accompanied by widespread gliosis, tissue death due to an infarction or loss of blood supply to the brain, and changes in the plasticity of the arteries. The pathologic mechanism may be damage caused by severe atherosclerosis. The onset of this disease is typically between 54 – 66 years of age and the first symptoms are usually mental deterioration or stroke.[4]
The vessels that supply the subcortical white matter come from the vessels that support basal ganglia, internal capsule, and thalamus. It is described as its own zone by and susceptible to injury. Chronic hypertension is known to cause changes in the tension of the smooth wall vessels and changes in the vessel diameter.[3] Arterioles can become permeable resulting in compromise of the blood brain barrier.[4][10] It has been shown that Binswanger's disease targets the vessels in this zone of the subcortex, but spares the microcirculation's vessels and capillaries which may be attributed to a difference between Alzheimer's and Binswanger's disease.[11]
### Psychiatric presentation[edit]
There is a difference between cortical and subcortical dementia. Cortical dementia is atrophy of the cortex which affects ‘higher’ functions such as memory, language, and semantic knowledge whereas subcortical dementia affects mental manipulation, forgetfulness, and personality/emotional changes. Binswanger's Disease has shown correlations with impairment in executive functions, but have normal episodic or declarative memory. Executive functions are brain processes that are responsible for planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting relevant sensory information. There have been many studies done comparing the mental deterioration of Binswanger patients and Alzheimer patients. It has been found in the Graphical Sequence Test that Binswanger patients have hyperkinetic perseveration errors which cause the patients to repeat motion even when not asked whereas Alzheimer patients have semantic perseveration because when asked to write a word they will instead draw an image depicting the word.[12]
## Diagnosis[edit]
Binswanger's disease can usually be diagnosed with a CT scan, MRI, and a proton MR spectrography in addition to clinical examination. Indications include infarctions, lesions, or loss of intensity of central white matter and enlargement of ventricles, and leukoaraiosis. A Mini–Mental State Examination (MMSE) has been created to quickly assess cognitive impairment and serves as a screening test for dementia across different cultures.[citation needed]
### Imaging[edit]
Leukoaraiosis (LA) refers to the imaging finding of white matter changes that are common in Binswanger disease. However, LA can be found in many different diseases and even in normal patients, especially in people older than 65 years of age.[5]
There is controversy whether LA and mental deterioration actually have a cause and effect relationship. Recent research is showing that different types of LA can affect the brain differently, and that proton MR spectroscopy would be able to distinguish the different types more effectively and better diagnosis and treat the issue.[9] Because of this information, white matter changes indicated by an MRI or CT cannot alone diagnose Binswanger disease, but can aid to a bigger picture in the diagnosis process. There are many diseases similar to Binswanger's disease including CADASIL syndrome and Alzheimer's disease, which makes this specific type of white matter damage hard to diagnose.[5] Binswanger disease is best when diagnosed of a team by experts including a neurologist and psychiatrist to rule out other psychological or neurological problems.[3] Because doctors must successfully detect enough white matter alterations to accompany dementia as well as an appropriate level of dementia, two separate technological systems are needed in the diagnosing process.[citation needed]
Much of the major research today is done on finding better and more efficient ways to diagnose this disease. Many researchers have divided the MRIs of the brain into different sections or quadrants. A score is given to each section depending on how severe the white matter atrophy or leukoaraiosis is. Research has shown that the higher these scores, the more of a decrease in processing speed, executive functions, and motor learning tasks.[13][14] Other researchers have begun using computers to calculate the percentage of white matter atrophy by counting the hyper-intense pixels of the MRI. These and similar reports show a correlation between the amount of white matter alterations and the decline of psychomotor functions, reduced performance on attention and executive control.[15][16] One recent type of technology is called susceptibility weighted imaging (SWI) which is a magnetic resonance technique which has an unusually high degree of sensitivity and can better detect white matter alterations.[17]
## Management[edit]
Binswanger's disease has no cure and has been shown to be the most severe impairment of all of the vascular dementias.[18] The best way to manage the vascular risk factors that contribute to poor perfusion in the brain is to treat the cause, such as chronic hypertension or diabetes. It has been shown that current Alzheimer's medication, donepezil (trade name Aricept), may help Binswanger's Disease patients as well[citation needed]. Donepezil increases the acetylcholine in the brain through a choline esterase inhibitor which deactivates the enzyme that breaks down acetylcholine.[3] Alzheimer as well as Binswanger patients have low levels of acetylcholine and this helps to restore the normal levels of neurotransmitters in the brain.[3] This drug may improve memory, awareness, and the ability to function.[19] If no medical interception of the disease is performed then the disease will continue to worsen as the patient ages due to the continuing atrophy of the white matter from whatever was its original cause.[3]
## History[edit]
Binswanger in 1894 was the first to claim that white matter atrophy caused by 'vascular insufficiency' can result in dementia. He described a patient who had slow progression of dementia as well as subcortical white matter atrophy, ventricle enlargement, aphasia, hemianopsia, and hemiparesis.[9] He named this disease 'encenphailitis subcorticalis chronica progressive.' Binswanger did not conduct any microscopic investigations so many did not believe his findings and attributed the neural damage to neural syphilis.[3] Alzheimer in 1902 studied Binswanger's work with pathological evidence that concluded and supported Binswanger's ideas and hypotheses. Alzheimer renamed this disease Binswanger's disease.[4]
In the late 19th century vascular dementia was heavily studied, however by 1910 scientists were lumping Binswanger's disease with all other subcortical and cortical dementia and labeling everything senile dementia despite all previous research and efforts to distinguish this disease from the rest. In 1962 J. Olszewski published an extensive review of all literature about Binswanger's disease so far. He discovered that some of the information in the original reports was incorrect and that at least some of the patients studied in these cases probably had neurosyphilis or other types of dementia. Even with these errors, Olszewski concluded that Binswanger disease did exist as a subset of cerebral arteriosclerosis.[18] Yet again, in 1974 the term multi-infarct dementia was coined and all vascular dementia was grouped into one category. Because of this, the specific names of these types of this dementia, including Binswanger's disease were lost.[4] This was until 1992 when Alzheimer's diagnostic centers created specific criteria known as the Hachinski Ischemic Scale (after Dr. Vladimir Hachinski) which became the standard for diagnosing MID or vascular dementia.[20]
The complicated history of Binswanger's disease and the fact that it was overlooked as a disease for many years means many patients may have been misdiagnosed with Alzheimer's disease.[9]
## References[edit]
1. ^ van der Knaap, MS; Valk, J (1995). "Subcortical Arteriosclerotic Encephalopathy". Magnetic resonance of myelin, myelination, and myelin disorders (2nd ed.). Berlin, Heidelberg: Springer. doi:10.1007/978-3-662-03078-3_65. ISBN 978-3-662-03078-3.
2. ^ Akiguchi I, Tomimoto H, Suenaga T, Wakita H, Budka H (1997). "Alterations in glia and axons in the brains of Binswanger's disease patients". Stroke. 28 (7): 1423–9. doi:10.1161/01.str.28.7.1423. PMID 9227695. Archived from the original on 2013-01-12.
3. ^ a b c d e f g h Giovannetti, T. Personal Interview. 16 October 2009
4. ^ a b c d e Libon, David; Price, C.; Davis Garrett, K.; T. Giovannetti (2004). "From Binswanger's Disease to Leukoaraiosis: What We Have Learned About Subcortical Vascular Dementia". The Clinical Neuropsychologist. 18 (1): 83–100. doi:10.1080/13854040490507181. PMID 15595361. S2CID 207733.
5. ^ a b c d e Loeb C (2000). "Binswanger's disease is not a single entity". Neurol. Sci. 21 (6): 343–8. doi:10.1007/s100720070048. PMID 11441570. S2CID 8914783. Archived from the original on 2013-01-04.
6. ^ Pantoni L, Moretti M, Inzitari D (1996). "The first Italian report on "Binswanger's disease"". Ital J Neurol Sci. 17 (5): 367–70. doi:10.1007/BF01999900. PMID 8933231. S2CID 22502909.
7. ^ "Review: Binswanger's disease, leuokoaraiosis and dementia". Age and Ageing. 1994. Retrieved 2008-01-30.
8. ^ Olszewski J (1962). "Subcortical arteriosclerotic encephalopathy. Review of the literature on the so-called Binswanger's disease and presentation of two cases". World Neurol. 3: 359–75. PMID 14481961.
9. ^ a b c d Libon, D., Scanlon, M., Swenson, R., and H. Branch Coslet(1990): "Binswanger's disease: some Neuropsychological Considerations", Journal of Geriatric Psychiatry and Neurology, 3(1):31-40.
10. ^ de Reuck, J. (1971). "The human periventricular arterial blood supply and anatomy of cerebral infarctions". European Neurology. 5 (6): 321–334. doi:10.1159/000114088. PMID 5141149.
11. ^ Kitaguchi, Hiroshi; Ihara, M.; Saiki, H.; Takahashi, R.; H. Tomimoto (1 May 2007). "Capillary beds are decreased in Alzheimer's disease, but not in Binswanger's disease". Neuroscience Letters. 417 (2): 128–131. doi:10.1016/j.neulet.2007.02.021. PMID 17403574. S2CID 42743797.
12. ^ Goldberg, E. (1986): “Varieties of perseveration: A comparison of two taxonomies.”, Journal of Clinical and Experimental Neuropsychology, 8:710-726.
13. ^ Junque, C.; Pujol, J.; Vendrell, P.; Bruna, O.; Jodar, M.; Ribas, J.C.; Vinas, J.; Capevila, A.; Marti-Wilalta, J.L. (1990). "Leukoaraiosis on magnetic resonance imaging and speed of mental processing". Archives of Neurology. 47 (2): 151–156. doi:10.1001/archneur.1990.00530020047013. PMID 2302086.
14. ^ Libon, David; Bogdanoff, B.; Cloud, B.S.; Skalina, S.; Carew, T.G.; Gitlin, H.L.; Bonavita, J. (1998). "Motor Learning and quantitative measures of the hippocampus and subcortical white alterations in Alzheimer's disease and Ischaemic Vascular Dementia". Journal of Clinical and Experimental Neuropsychology. 20 (1): 30–41. doi:10.1076/jcen.20.1.30.1490. PMID 9672817.
15. ^ Davis-Garrett, K.L.; Cohen, R.A.; Paul, R.H.; Moser, D.J.; Malloy, P.F.; Shah, P. (2004). "Computer-mediated measurement and subjective ratings of white matter hyperintensities in vascular dementia: Relationships to neuropsychological performance. I". The Clinical Neuropsychologist. 18 (1): 50–62. doi:10.1080/13854040490507154. PMID 15595358. S2CID 28474962.
16. ^ Moser, D.J.; Cohen, R.A.; Paul, R.H.; Paulsen, J.S.; Ott, B.R.; Gordon, N.M.; Bell, S.; Stone, W.M. (2001). "Executive function and magnetic resonance imaging subcortical hyperintensities in Vascular dementia". Neuropsychiatry, Neuropsychology & Behavioral Neurology. 14 (2): 89–92. PMID 11417671.
17. ^ Santhosh, K.; Kesavadas, C.; Thomas, B.; Gupta, A.K.; Thamburaj, K.; T. Raman Kapilamoorthy (January 2009). "Susceptibility weighted imaging: a new tool in magnet resonance imaging of stroke". Clinical Radiology. 64 (1): 74–83. doi:10.1016/j.crad.2008.04.022. PMID 19070701.
18. ^ a b Thajeb, Peterus; Thajeb, T.; and D. Dai (March 2007). "Cross-cultural studies using a modified mini mental test for healthy subjects and patients with various forms of vascular dementia". Journal of Clinical Neuroscience. 14 (3): 236–241. doi:10.1016/j.jocn.2005.12.032. PMID 17258132. S2CID 22115410.
19. ^ "Aricept". Retrieved 2009-11-30.
20. ^ Hachinski, V.C., Iliff, L.D., Zilhka, E., Du Boulay, G.H., McAllister, V.L., Marshall, J., Russell, R.W.R., and Symon, L. (1975): “Cerebral blood flow in dementia”, Archives of Neurology, 32:632-7.
## External links[edit]
Classification
D
* ICD-10: I67.3
* ICD-9-CM: 290.12
* MeSH: D015140
* DiseasesDB: 1405
* v
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Mental and behavioral disorders
Adult personality and behavior
Gender dysphoria
* Ego-dystonic sexual orientation
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Symptoms and uncategorized
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* v
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Cerebrovascular diseases including stroke
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Classification
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Other
* CADASIL
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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
| Binswanger's disease | c0270786 | 2,363 | wikipedia | https://en.wikipedia.org/wiki/Binswanger%27s_disease | 2021-01-18T18:43:20 | {"gard": ["5925"], "mesh": ["D015140"], "icd-9": ["290.12"], "icd-10": ["I67.3"], "wikidata": ["Q1399293"]} |
A severe form of lissencephaly with cerebellar hypoplasia, characterized by a microcephaly of at least - 3 SD and a thick cortex associated with complete absence of the corpus callosum.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Lissencephaly with cerebellar hypoplasia type F | c4274989 | 2,364 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100016 | 2021-01-23T17:36:48 | {"icd-10": ["Q04.3"]} |
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (December 2014) (Learn how and when to remove this template message)
Medical fetishism refers to a number of sexual fetishes involving objects, practices, environments, and situations of a medical or clinical nature. In sexual roleplay a hospital or medical scene involves the sex partners assuming the roles of doctors, nurses, surgeons and patients to act out specific or general medical fetishes. Medical fantasy is a genre in pornography, though the fantasy may not necessarily involve pornography or sexual activity.
Medical fetishism may involve sexual attraction to respiratory therapy involving oxygen via nasal cannula or any sort of masks, medical practitioners, medical uniforms, hospital gowns, anaesthesia, intimate examinations (such as rectal examination, gynecological examination, urological examination, andrological examination, rectal temperature-taking), catheterization, diapering, enemas, injections, insertion (such as suppository insertion, menstrual-cup insertion, and prostatic massage), medical devices (such as orthopedic casts and orthopedic braces; see also "Abasiophilia"), dental objects (such as dental braces, retainers, and headgear), medical restraints, and medical gags.
## Contents
* 1 Physical examination
* 2 Temperature-taking fetishism
* 3 Enema fetishism
* 4 Anesthesia fetishism
* 4.1 Acts, behaviour and rituals
* 4.2 Internet influence
* 5 See also
* 6 References
* 7 Bibliography
## Physical examination[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. (March 2019) (Learn how and when to remove this template message)
The film set for a medical fetishism scene
Some people eroticize about intimate examinations as part of a medical fetish, and as such are a common service offered by professional dominants.
An intimate examination can form part of a scene in medical play where the nurse or doctor (or even or a nun)[1] inflicts one or more embarrassing and humiliating quasi-medical procedures on the patient. Often frozen or heated objects are introduced to the patient's body to simulate the uncomfortable sensations that can occur during a real examination. Examinations may include an examination and intrusion of the anus, urethra, or vagina, as well as handling and twisting of the penis, testicles, clitoris, and nipples. Quite often, strap on play is also incorporated, as this can heighten the intimacy, and also the sensations of the "patient" (recipient). This may be a prelude to masturbation or administration of an enema. Before examination, the patient can be placed in physical restraints and gagged, and wear some form of embarrassing clothing.
## Temperature-taking fetishism[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. (August 2020) (Learn how and when to remove this template message)
Temperature-taking fetish is a sexual fetish for oral and rectal thermometers. This may include the sexual attraction to the equipment, processes, environments, or scenarios/situations. The fetish is characterized by sexual arousal from the desire to take another person's temperature or have one's temperature taken. Although there is also an interest in oral temperature taking, rectal temperature taking is more prominent and often precedes enema play.[citation needed]
## Enema fetishism[edit]
This section needs expansion. You can help by adding to it. (July 2020)
Enema fetishism is a sexual fetish for enemas and is a type of klismaphilia which is the general enjoyment of enemas. This fetish includes not only giving and receiving enemas but also sexual attraction to the equipment, processes, environments, situations, or scenarios,[1] and some may be sexually aroused by the preparations, such as by the feel and smell of a latex rubber or plastic syringe, by the smell of soapsuds enema solution, or by preparing the recipient.[2] Role playing often accompanies these activities.[1]
Enemas can cause sexual arousal in both women and men because the bulbospongiosus muscle which starts in front of the anus contributes, in women, to clitoral erection and the contractions of orgasm, and closes the vagina, and in men, to erection, the contractions of orgasm, and ejaculation. Sexual sensation results from distention of the rectum by filling and dilating it with the volume of an enema which, in women, puts pressure on the back of the vagina, and in men stimulates the prostate and seminal vesicles.[3] Also, contractions of muscles throughout the abdomen caused by expulsion of an enema can stimulate, in women, the uterus and vagina, and in men, the prostate, seminal vesicle, and internal penis.[2]
Enemas are also, however, very embarrassing, with the exposure and probing of the most private of body parts, the anus. An erotic enema holds the possibility of acting out vulnerability in a primal form. Among the attractions to enema play are psychodrama, power exchange, erotic humiliation, discipline, and so on.[1] BDSM punishment scenes can use extra-large volumes or highly irritating substances to produce pain and cramps.[3]
## Anesthesia fetishism[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. (March 2019) (Learn how and when to remove this template message)
Anesthesia fetishism is a sexual fetish for anesthesia. This may include the sexual attraction to the equipment, processes, substances, effects, environments or situations. Sexual arousal from the desire to administer anesthesia, or the sexual desire for oneself to be anesthetized are two forms in which an individual may exist as an arbiter of the fetish. Older-style anesthesia masks of black rubber, still in occasional use today, are one of the more common elements fetishized, and have earned the nickname Black Beauty by many fetishists.
### Acts, behaviour and rituals[edit]
Anesthesia fetish is considered edgeplay when realised outside the boundaries of fantasy, and may result in various degrees of harm, or death. Fantasies are elaborated by the viewing of images and reading of stories of anesthetic inductions. Edgeplay may involve obtaining and scening with various anesthesia-related paraphernalia—usually anesthesia masks for breathplay, the acquisition of anesthetics for anesthetizing others or being anesthetized oneself, and the occupation of a medical setting or environment for the same practice.
Some anesthesia fetishists who seek to be anesthetized may feign or induce medical conditions in an attempt to obtain general anesthesia from medical personnel. This is considered safer than playing with anesthetic agents outside of a medical setting.
### Internet influence[edit]
The Internet has enabled people with this relatively rare paraphilia to discuss the subject and exchange anesthesia-related multimedia.[citation needed]
## See also[edit]
Wikimedia Commons has media related to Medical fetishism.
* Playing doctor
* Paraphilia
* Amputation fetishism
* Klismaphilia
* List of fictional nurses
## References[edit]
1. ^ a b c d Brame, Gloria; Brame, William D.; Jacobs, Jon (1993). Different Loving – The World of Sexual Dominance and Submission. Villard Books. ISBN 978-0-6797-6956-9.
2. ^ a b Agnew, J. (2000). "Klismaphilia". Venereology. 13 (2): 75–79. ISSN 1032-1012. Retrieved 22 July 2020.
3. ^ a b Agnew, J. (October 1982). "Klismaphilia--a physiological perspective". American Journal of Psychotherapy. 36 (4): 554–566. doi:10.1176/appi.psychotherapy.1982.36.4.554. ISSN 0002-9564. PMID 7158678.
## Bibliography[edit]
* Gary L. Albrecht, "Encyclopedia of disability, Volume 2", Sage Publications, 2006, ISBN 0-7619-2565-1, p. 1437
* Midori, "Wild Side Sex: The Book of Kink Educational, Sensual, And Entertaining Essays", Daedalus Publishing, 2005, ISBN 1-881943-22-4, p. 211
* v
* t
* e
Sexual fetishism
Actions, states
* Aquaphilia
* Autassassinophilia
* Coprophilia
* Cuckold / Cuckquean
* Emetophilia
* Erotic hypnosis
* Erotic lactation
* Erotic spanking
* Exhibitionism
* Forced seduction
* Gaining and feeding
* Medical fetishism
* Omorashi
* Paraphilic infantilism (adult baby)
* Pregnancy
* Smoking
* Tickling
* Total enclosure
* Transvestic
* Tightlacing
* Tamakeri
* Urolagnia
* Vorarephilia
* Wet and messy fetishism
Body parts
* Armpit
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* Buttocks
* Eyeball
* Fat
* Feet
* Hands
* Height
* Hair
* Legs
* Navels
* Noses
Clothing
* Boots
* Ballet boots
* Boot worship
* Thigh-high boots
* Clothing
* Corset
* Diapers
* Gloves
* Pantyhose
* Latex
* Rubber and PVC
* Shoes
* Spandex
* Underwear
* Uniforms
Objects
* Balloons
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* Latex and PVC
* Robots
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Controversial / illegal
* Lust murder
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* Rape fantasy
* Zoophilia
Culture / media
* Artists
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* Fashion
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Race
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Related topics
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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
| Medical fetishism | None | 2,365 | wikipedia | https://en.wikipedia.org/wiki/Medical_fetishism | 2021-01-18T18:29:57 | {"wikidata": ["Q1413869"]} |
This article is about oral exposure to zinc. For inhalation toxicity, see Metal fume fever.
Zinc toxicity
Zinc
SpecialtyEmergency medicine
Zinc toxicity is a medical condition involving an overdose on, or toxic overexposure to, zinc. Such toxicity levels have been seen to occur at ingestion of greater than 50 mg of zinc.[1][unreliable medical source?] Excessive absorption of zinc can suppress copper and iron absorption. The free zinc ion in solution is highly toxic to bacteria, plants, invertebrates, and even vertebrate fish.[2][3][4] Zinc is an essential trace metal with very low toxicity in humans.[1][5]
## Contents
* 1 Signs and symptoms
* 2 High levels of intake by humans
* 3 Cross-reaction toxicity
* 4 Diagnosis
* 5 Treatment
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Following an oral intake of extremely high doses of zinc (where 300 mg Zn/d – 20 times the US RDA – is a "low intake" overdose[1]), nausea, vomiting, pain, cramps and diarrhea may occur.[1] There is evidence of induced copper deficiency, alterations of blood lipoprotein levels, increased levels of LDL, and decreased levels of HDL at long-term intakes of 100 mg Zn/d.[1] The USDA RDA is 15 mg Zn/d.[1]There is also a condition called the "zinc shakes" or "zinc chills" or metal fume fever that can be induced by the inhalation of freshly formed zinc oxide formed during the welding of galvanized materials.[6]
## High levels of intake by humans[edit]
Zinc has been used therapeutically at a dose of 150 mg/day for months and in some cases for years, and in one case at a dose of up to 2000 mg/day zinc for months.[7][8][9][10][11] A decrease in copper levels and hematological changes have been reported; however, those changes were completely reversed with the cessation of zinc intake.[9]
However, zinc has been used as zinc gluconate and zinc acetate lozenges for treating the common cold[12] and therefore the safety of usage at about 100 mg/day level is a relevant question. Thus, given that doses of over 150 mg/day for months to years has caused no permanent harm in many cases, a one-week usage of about 100 mg/day of zinc in the form of lozenges would not be expected to cause serious or irreversible adverse health issues in most individuals.
Unlike iron, the elimination of zinc is concentration-dependent.[13]
## Cross-reaction toxicity[edit]
Supplemental zinc can prevent iron absorption, leading to iron deficiency and possible peripheral neuropathy, with loss of sensation in extremities. Zinc and iron should be taken at different times of the day.[14]
## Diagnosis[edit]
Zinc concentrations are typically quantified using instrumental methods such as atomic absorption, emission, or mass spectroscopies; x-ray fluorescence; electro-analytical techniques (e.g., stripping voltammetry); and neutron activation analysis. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) is used for zinc determinations in blood and tissue samples (NIOSH Method 8005) and in urine (NIOSH Method 8310). Detection limits in blood and tissue are 1 µg/100 g and 0.2 µg/g, respectively, with recoveries of 100% (NIOSH 1994). Sample preparation involves acid digestion with concentrated acids. Detection of zinc in urine samples requires extraction of the metals with a polydithiocarbamate resin prior to digestion and analysis (NIOSH 1984). Detection limits in urine are 0.1 µg/sample.
## Treatment[edit]
This section is empty. You can help by adding to it. (November 2019)
## See also[edit]
* Zinc deficiency
## References[edit]
1. ^ a b c d e f Fosmire GJ (February 1990). "Zinc toxicity". Am. J. Clin. Nutr. 51 (2): 225–7. doi:10.1093/ajcn/51.2.225. PMID 2407097.
2. ^ Rout, Gyana Ranjan; Das, Premananda (1 January 2003). "Effect of Metal Toxicity on Plant Growth and Metabolism: I. Zinc" (PDF). Agronomie. 23 (1): 3–11. doi:10.1051/agro:2002073.
3. ^ SMITH, SE; LARSON, EJ (April 1946). "Zinc toxicity in rats; antagonistic effects of copper and liver". The Journal of Biological Chemistry. 163: 29–38. PMID 21023625.
4. ^ Brita, T. A.; De Schamphelaere, Muyssen; Karel, A. C.; Janssen, Colin R. (2006). "Mechanisms of chronic waterborne Zn toxicity in Daphnia magna". Aquatic Toxicology. 77 (4): 393–401. doi:10.1016/j.aquatox.2006.01.006. PMID 16472524.
5. ^ Ciubotariu D, Ghiciuc CM, Lupușoru CE (2015). "Zinc involvement in opioid addiction and analgesia - should zinc supplementation be recommended for opioid-treated persons?". Subst Abuse Treat Prev Policy. 10 (1): 29. doi:10.1186/s13011-015-0025-2. PMC 4523930. PMID 26238243.
6. ^ Pettilä, V.; Takkunen, O.; Tukiainen, P. (2000). "Zinc chloride smoke inhalation: a rare cause of severe acute respiratory distress syndrome". Intensive Care Medicine. 26 (2): 215–217. doi:10.1007/s001340050049.
7. ^ Pories, W.J. (1967). "Acceleration of healing with zinc sulfate". Ann Surg. 165: 432–6. doi:10.1097/00000658-196703000-00015. PMC 1617499. PMID 6019319.
8. ^ Simkin, P.A. (1976). "Oral zinc sulphate in rheumatoid arthritis". Lancet. 2: 539–42. doi:10.1016/s0140-6736(76)91793-1. PMID 60622.
9. ^ a b Samman, S.; Roberts, D.C. (1987). "The effect of zinc supplements on plasma zinc and copper levels and the reported symptoms in healthy volunteers". Med J Aust. 146: 246–9. PMID 3547053.
10. ^ Forman, W.B. (1990). "Zinc abuse: an unsuspected cause of sideroblastic anemia". West J Med. 152: 190–2. PMC 1002314. PMID 2400417.
11. ^ Fiske, D.N. (1994). "Zinc-induced sideroblastic anemia: report of a case, review of the literature, and description of the hematologic syndrome". Am J Hematol. 46 (2): 147–50. doi:10.1002/ajh.2830460217. PMID 8172183.
12. ^ Hemilä, H. (2011). "Zinc lozenges may shorten the duration of colds: a systematic review". Open Respir Med J. 5 (1): 51–8. doi:10.2174/1874306401105010051. PMC 3136969. PMID 21769305. Archived from the original on October 31, 2015.
13. ^ Lim KH, Riddell LJ, Nowson CA, Booth AO, Szymlek-Gay EA (2013). "Iron and zinc nutrition in the economically-developed world: a review". Nutrients. 5 (8): 3184–211. doi:10.3390/nu5083184. PMC 3775249. PMID 23945676. "Homeostatic regulation of iron and zinc differ, with iron being regulated through absorption and zinc being regulated primarily through secretion. As the body does not have a means to eliminate excess iron, absorption from the small intestine is tightly regulated by hepcidin. Hepcidin is a peptide hormone that is present in higher concentrations when body iron is replete [52]. Higher concentrations of hepcidin prevent ingested iron from entering the bloodstream by trapping iron in enterocytes which are naturally shed every two days [112], thereby preventing body iron from escalating to dangerous levels. In comparison, endogenous (pancreatic, biliary and intestinal) secretions comprise the main route of zinc loss, with larger zinc intakes being balanced by larger zinc secretions [113,114]."
14. ^ https://labdoor.com/article/a-guide-to-timing-supplement-intake
## External links[edit]
Classification
D
* ICD-10: T56.5
* ICD-9-CM: 985.8
* v
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1 including venoms, toxins, foodborne illnesses.
* Category
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Zinc toxicity | None | 2,366 | wikipedia | https://en.wikipedia.org/wiki/Zinc_toxicity | 2021-01-18T19:05:39 | {"icd-9": ["985.8"], "icd-10": ["T56.5"], "wikidata": ["Q10724674"]} |
Fibrous dysplasia is a skeletal disorder that is characterized by the replacement of normal bone with fibrous bone tissue. It may involve one bone (monostotic) or multiple bones (polyostotic). Fibrous dysplasia can affect any bone in the body. The most common sites are the bones in the skull and face, the long bones in the arms and legs, the pelvis, and the ribs. Though many people with this disorder do not have any symptoms, others may have bone pain, abnormally shaped bones (deformities), or an increased risk of fractures (broken bones). The problems a person experiences depend on which bones are affected, and may arise from compression and displacement of adjacent structures to the lesions. For example, the legs can be of different lengths, leading to a limp, the bones of the sinuses can be affected, leading to chronic sinus congestion or headache. This condition can occur alone or as part of a genetic disorder, such as McCune-Albright syndrome. While there is no cure for fibrous dysplasia, the symptoms can be treated. Medications known as bisphosphonates can reduce pain and surgery may be used to treat fractures or to correct misshapen bones.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Fibrous dysplasia | c0259779 | 2,367 | gard | https://rarediseases.info.nih.gov/diseases/6444/fibrous-dysplasia | 2021-01-18T18:00:29 | {"umls": ["C0259779"], "orphanet": ["249"], "synonyms": ["Fibrous dysplasia of bone"]} |
An X-linked intellectual disability syndrome with neuromuscular involvement characterized by infantile hypotonia, muscular hypoplasia, spastic paraparesis with dystonic/athetoic movements, and severe cognitive deficiency.
## Epidemiology
At least 132 families with 320 affected individuals have been reported in the literature to date. Although the prevalence is unknown, one study identified AHDS in 1.4% of males with intellectual disability of unknown etiology. Only males are affected.
## Clinical description
The disease manifests as congenital hypotonia (appearing at birth or in the first weeks/months of life) that progresses to spasticity (contractures, Babinski sign, and clonus), and is usually detectable early in life. Hyperreflexia appears later in life. Affected males also present, in infancy and early childhood, with muscle hypoplasia and generalized muscle weakness that manifests as difficulty in supporting the head and delayed motor milestones. Hypotonia and severe intellectual deficit are present in 100% of patients. Severe psychomotor delay is present from the outset (delay of motor and language milestones) and autonomy is never reached. The face has distinctive features that evolve over time: open mouth, tented upper lip, ptosis, abnormal folding of the ears, thickening of the soft tissue of the nose and ears, and upturned earlobes. Long, thin everted feet are also typical. Ocular manifestations (i.e. rotary nystagmus and disconjugate eye movements) are rare. Seizures and poor weight gain are reported in some patients. Pectus excavatum and scoliosis are sometimes present, perhaps as a result of the hypotonia and muscle hypoplasia.
## Etiology
AHDS is caused by mutations in the SLC16A2 gene (Xq13.2), which encodes for monocarboxylate transporter 8 (MCT8), a specific transporter for thyroid hormone T3. Identified mutations include truncations, in-frame deletions, nonsense and missense mutations. Neurological problems may be due to an inability to transport thyroid hormone T3 into some neuronal cells.
## Diagnostic methods
Diagnosis is based on clinical findings and on the presence of altered thyroid- hormone serum levels: males have abnormally high 3,3',5'-triiodothyronine (T3), low to normal free tetraiodothyronine (T4) levels, and normal to slightly elevated thyroid stimulating hormone (TSH) levels. Molecular genetic testing revealing mutations in the SLC16A2 gene confirms the diagnosis.
## Differential diagnosis
Differential diagnoses include X-linked intellectual disability conditions associated with ataxia, spastic paraplegia or muscle hypoplasia such as X-linked intellectual disability-spastic paraplegia with iron deposits syndrome, X-linked progressive cerebellar ataxia, and spastic paraplegia type 2. Pelizaeus-Merzbacher disease and Snyder-Robinson syndrome should also be considered.
## Antenatal diagnosis
Antenatal diagnosis of a male with AHDS is possible if the mother is a carrier of a specific SLC16A2 mutation.
## Genetic counseling
Transmission is X-linked recessive. Affected families should be offered genetic counseling and informed that boys have a 50% risk of being affected if the mother is a carrier of a SLC16A2 mutation and that girls have a 50% risk of inheriting the SLC16A2 mutation if their mother is a SLC16A2 mutation carrier.
## Management and treatment
At present, no treatment is available for AHDS and management consists of supportive measures. Physical, occupational, and speech therapy may be beneficial. Dystonia may be treated with certain medications, including anticholinergics, L-DOPA, carbamazepine, or lioresol. Seizures, when present, can be controlled with standard antiepileptic drugs. Treatment for hypothyroidism does not appear to be beneficial.
## Prognosis
Although several patients have survived into their 60s, overall life expectancy is compromised and quality of life is severely affected as most patients are unable to sit, stand or walk independently.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Allan-Herndon-Dudley syndrome | c0795889 | 2,368 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=59 | 2021-01-23T18:05:21 | {"gard": ["5617"], "mesh": ["C537047"], "omim": ["300523"], "umls": ["C0795889"], "icd-10": ["G31.8"], "synonyms": ["AHDS", "MCT8 deficiency", "Monocarboxylate transporter 8 deficiency", "X-linked intellectual disability-hypotonia syndrome"]} |
Group of disorders
Epstein–Barr virus-associated lymphoproliferative diseases
Other namesEBV-associated lymphoproliferative diseases
SpecialtyHematology, oncology, Infectious disease, virology
CausesEpstein–Barr virus
Epstein–Barr virus-associated lymphoproliferative diseases (also termed EBV-associated lymphoproliferative diseases or EBV+ LPD) are a group of disorders in which one or more types of lymphoid cells (a type of white blood cell), i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.[1]
EBV-associated LPDs are a subcategory of EBV-associated diseases. Non-LPD that have significant percentages of cases associated with EBV infection (see Epstein–Barr virus infection) include the immune disorders of multiple sclerosis and systemic lupus erythematosus;[2] malignancies such as stomach cancers,[3] soft tissue sarcomas, leiomyosarcoma, and undifferentiated nasopharyngeal cancer;[4] the childhood disorders of Alice in Wonderland syndrome;[5] and acute cerebellar ataxia.[6]
About 95% of the world's population is infected with EBV. During the initial infection, the virus may cause infectious mononucleosis, only minor non-specific symptoms, or no symptoms. Regardless of this, the virus enters a latency phase in its host and the infected individual becomes a lifetime asymptomatic carrier of EBV. Weeks, months, years, or decades thereafter, a small percentage of these carriers, particularly those with an immunodeficiency, develop an EBV+ LPD. Worldwide, EBV infection is associated with 1%[7] to 1.5%[8] of all cancers.[1] The vast majority of these EBV-associated cancers are LPD. The non-malignant, premalignant, and malignant forms of EBV+ LPD have a huge impact on world health.[1]
The classification and nomenclature of the LPD reported here follow the revisions made by the World Health Organization in 2016. This classification divides EBV+ LPD into five categories: EBV-associated reactive lymphoid proliferations, EBV-associated B cell lymphoproliferative disorders, EBV-associated NK/T cell lymphoproliferative disorders, EBV-associated immunodeficiency-related lymphoproliferative disorders, and EBV-associated histiocytic-dendritic disorders.[9]
## Contents
* 1 Pathophysiology
* 1.1 Lymphoid cells involved in EBV+ LPD
* 1.2 Epstein–Barr virus infection
* 2 EBV-associated reactive lymphoid proliferations
* 2.1 Epstein-Barr virus-positive reactive lymphoid hyperplasia
* 2.2 Epstein–Barr virus-positive infectious mononucleosis
* 2.3 Epstein–Barr virus-related hemophagocytic lymphohistiocytosis
* 2.4 Chronic active Epstein–Barr virus infection
* 2.4.1 Severe mosquito bite allergy
* 2.4.2 Hydroa vacciniforme-like lymphoproliferative disease
* 2.5 Epstein–Barr virus-positive mucocutaneous ulcer
* 3 EBV+ B cell lymphoproliferative diseases
* 3.1 Epstein–Barr virus-positive Burkitt lymphoma
* 3.2 Epstein–Barr virus-positive lymphomatoid granulomatosis
* 3.3 Epstein–Barr virus-positive Hodgkin lymphoma
* 3.4 Epstein–Barr virus-positive diffuse large B cell lymphoma, not otherwise specified
* 3.4.1 Epstein–Barr virus-associated diffuse large B cell lymphoma associated with chronic inflammation
* 3.4.1.1 Fibrin-associated diffuse large B cell lymphoma
* 3.5 Epstein–Barr virus-positive human herpes virus 8-associated B cell lymphoproliferative disorders
* 3.5.1 Primary effusion lymphoma
* 3.5.2 Epstein–Barr virus-positive, human herpes virus-positive germinotropic lymphoproliferative disorder
* 3.6 Epstein–Barr virus-positive plasmablastic lymphoma
* 3.7 Epstein–Barr virus-associated plasma cell myeloma
* 4 EBV+ NK/T cell lymphoproliferative diseases
* 4.1 Peripheral T-cell lymphomas
* 4.1.1 Extranodal NK/T cell lymphoma, nasal type
* 4.1.2 Epstein–Barr virus-associated peripheral T cell lymphoma, not otherwise specified
* 4.1.3 Angioimmunoblastic T cell lymphoma
* 4.1.3.1 Follicular T cell lymphoma
* 4.2 Systemic Epstein–Barr virus-positive T cell lymphoma of childhood
* 4.3 Epstein–Barr virus-associated aggressive NK cell leukemia
* 4.4 Intravascular NK/T-cell lymphomas
* 5 EBV-associated immunodeficiency-related lymphoproliferative disorders
* 5.1 EBV-related and HIV-related LPD
* 5.2 Post-transplant lymphoproliferative disorders
* 6 EBV-associated histiocytic-dendritic disorders
* 6.1 Inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma
* 7 References
## Pathophysiology[edit]
### Lymphoid cells involved in EBV+ LPD[edit]
In the "germinal center model" for the normal maturation of B cells, naive B cells enter the germinal centers of lymph nodes and other lymphoid tissues and in the process of becoming competent for producing functional antibodies, mature into lymphoblasts, centroblasts, centrocytes, memory B cells, and ultimately plasma cells. During this maturation, the B cells rearrange their immunoglobulin genes at multiple sites.[8] The first lymphoid cell type invaded by EBV is the naïve B cell. Following this invasion, the virus express genes that control this cell's advance through these maturation stages; it can force the naïve B cell that it infects to: arrest maturation at any of these stages; become undetectable as an infected cell by the host's immune system; proliferate excessively; and develop into a B cell-based LPD. The virus may also exit the B cell it initially infects; invade T- or NK cells; and cause these cells to avoid detection by the immune system, proliferate, and progress to a T- or NK cell-based LPD.[10] The T cells that may become infected by EBV are natural killer T cells (NK cells), Gamma delta T cells (γδ T cells), cytotoxic T cells (CTL), helper T cells (Th cells), and follicular B helper T cells (TFH cells).[11] The means by which EBV establishes an dendritic-histiocytic cell (i.e. follicular dendritic cell) infection are unclear. Follicular dendritic cells are connective tissue rather than lymphoid cells. They do, however, have a surface membrane receptor, CD21 (also known as complement receptor type 2), which EBV uses to enter B cells. EBV may escape their infected B cell to invade follicular dendritic cells through this CD21 entry pathway. However, it is also thought possible that the EBV may direct its infected lymphoid cell to mature into an apparent follicular dendritic cell.[12]
### Epstein–Barr virus infection[edit]
Main article: Epstein–Barr virus § Replication cycle
The Epstein-Barr virus (also termed human herpesvirus 4) belongs to the Herpes family of Group I double-stranded DNA viruses. It is spread by transfer from the oral/nasal secretions of an infected individual to the oral cavity of an uninfected individual. Once in the oral cavity, the virus invades, reproduces in, establishes its lytic phase in, and lyses (i.e. bursts open) epithelial cells that line the oral mucosa of the newly infected individual. The freed virus then invades naïve B cells located in submucosal lymphoid tissue e.g. tonsils or adenoids. Here, it establishes either a lytic phase that allows it to infect other lymphoid cells or expresses genes that suppress the lytic cycle and impose one of four latency phases. Initially, the virus establishes latency III by expressing nuclear proteins encoded by its EBNA-1, -2, -3A, -3B, -3C, LP, LMP-1, -2A, and -2B and BART genes; cell surface membrane proteins encoded by its LMP-1, -2A, and 3A genes; and microRNAs encoded by its EBER-1 and EBER-2 genes. The products of these genes immortalize, promote the growth and survival, and regulate the maturation of the infected B cell. However, products of some latency III genes (particularly the viral cell surface proteins) make the infected cell susceptible to attack by the host's immune system. The virus avoids this by limiting expression of its latency genes to EBNA-1, LMP-1, -2A, -2B, some BARTs, and the two EBERs. This Latency II pattern of gene expression continues the infected cells' immortalization and proliferation, helps the cells escape the immune surveillance, and forces them to differentiate (i.e. mature) into memory B cells. EBV may establish and maintain a Latency I state in its infected memory B cells by expressing only EBNA1 and the two EBER genes. The products of the latter genes keep the virus in a mostly dormant state. Finally, EBV may establish and maintain a Latency 0 phase by expressing only EBER genes. In latency 0, EBV is in memory B cells as fully dormant, non-reproductive viruses but in this, as in all of the other latency phases, it can revert to its lytic phase.[8] The following table gives more information on the actions of the EBV latency genes.
EBV product Latency Function
EBNA-1 III, II, I Promote replication of the viral genome;[8] controls the infected cell's expression of nuclear and surface membrane proteins that regulate the virus's latency phases.[1]
EBNA-2 III Induces expression of the virus's LMP gene and ~300 genes of the infected cell (e.g. the MYC proto-oncogene) which promote this cell's proliferation, survival, and malignancy;[8] required for the malignant transformation of this cell.[1]
EBNA-3A III Represses expression of the infected cell's p16INK4a protein thereby promoting its proliferation; represses expression the infected cell's BCL2L11 protein thereby inhibiting apoptosis to promote this cell's survival.[8]
EBNA-3B III Inhibits the infected cell's proliferation; attracts lymphoid cells to its infected cell; inactivates promoters of its infected cell's genes possibly thereby causing this cell more able to evade the host's immune system and to become malignant.[1]
EBNA-3C III Required for the malignant transformation of infected cells; along with EBNA-3A, represses the infected cell's p16INK4a and BCL2L11 proteins thereby promoting, respectively, this cell's proliferation and repressing its apoptosis;[8] disturbs cell cycle checkpoints in the infected cell to promote its proliferation or locking it in the non-reproductive cell cycle state of G1.[1]
EBNA-LP III Overcomes the innate immune responses of infected cells to promote the virus's survival;[8] acts with EBNA-2 to promote the malignant transformation of its infected cells.[1]
LMP-1 III, II Induces the expression of the infected cell's NF-κB and BCL2 proteins thereby blocking this cells apoptosis and stimulating its proliferation; regulates the infected cell's maturation.[8]
LMP-2A III, II Prevents the establishment of EBV's lytic cycle;[1] stimulates the infected cell's AKT and B cell receptor proteins thereby blocking this cell's apoptosis and promoting its survival and proliferation.[8]
LMP-2B III, II Inhibits the ability of the virus's LMP-2A protein to establish EBV's lytic cycle; stimulates the infected host cell's AKT and B cell receptor proteins thereby blocking this cell's apoptosis and promoting its survival and proliferation.[1]
BART microRNAs III, II, I While abundantly expressed, the functions of BART microRNAs are unclear;[13] may help evade the infected cell avoid attack by uninfected T- and NK-cells[8] or modify the infected cell's notch signaling pathway to promote its proliferation; not required for EBV-induced B cell immortalization or malignant transformation.[1]
EBER1/2 nucelar RNAs III, II, I, 0 Abundantly expressed by EBV-infected cells in all latency stages; causes infected cell to produce interleukin 10 which may promote this cell to proliferate and avoid attack by host cytotoxic T cells;[1] may block apoptosis in the infected cell.[14]
## EBV-associated reactive lymphoid proliferations[edit]
EBV-associated reactive lymphoid proliferations are a set of disorders in which B cells or NK/T cells proliferate as an apparent reaction to EBV infection. They are usually self-limiting, non-malignant disorders but have a variable possibility of progressing to a malignant lymphoproliferative disease.[1]
### Epstein-Barr virus-positive reactive lymphoid hyperplasia[edit]
EBV-positive reactive lymphoid hyperplasia (or EBV-positive reactive lymphoid proliferation) is a benign form of lymphadenopathy, i.e. swollen, often painful lymph nodes. The disorder is based on histologic findings that occur in the lymphoid tissue of mainly older individuals who were infected with EBV many years earlier. Immunodeficient individuals of any age may also suffer the disorder. In immunologically normal individuals, histologic findings include the presence of small B cells located in the extrafollicular or, rarely, the follicular area of normal or minimally hyperplastic lymph nodes. These cells are commonly EBV+, express EBER viral genes, and carry the virus in its latency I or II phase. These cells may also occur in the bone marrow. Individuals who are immunodeficient because of disease, immunosuppressive drugs, or old age immunosenescence may exhibit a more pronounced hyperplasia of affected nodes, higher numbers of EBV+ cells, and a more disseminated disorder termed polymorphic lymphoproliferative disorder.[1] These disorders almost always resolve spontaneously but in very rare cases progress over months or years to EBV+ Hodgkin lymphoma or EBV+ diffuse large B-cell lymphoma of the elderly.[15]
### Epstein–Barr virus-positive infectious mononucleosis[edit]
Main article: Infectious mononucleosis
Infectious mononucleosis (IM) is caused by EBV in ~90% of cases; the remaining cases are caused by human cytomegalovirus, adenovirus, or toxoplasma.[16] HIV, rubella, and Hepatitis viruses A, B, and C can produce an illness resembling IM. The acute EBV infection is usually asymptomatic or mild in children <5 years old whereas 25–75% of adolescents and adults develop overt IM after infection.[10] The signs and symptoms of IM occur within weeks of EBV infection. Most cases involve a self-limiting flu-like illness or a mild to moderate illness of fever, sore throat, enlarged, painful lymph nodes in the head and neck, and/or an enlarged spleen. These manifestations usually abate within 6 weeks. More severe cases persist beyond 6 weeks and may be accompanied by uncommon but serious complications such as hepatitis, anemia, thrombocytopenia, hemophagocytosis, meningoencephalitis, myocarditis, pericarditis, pneumonitis, parotitis, pancreatitis[16] and, in rare but extremely severe cases, life-threatening complications such as rupture or the spleen or disease-transitions to other LPD such as hemophagocytic lymphohisiocytosis (HLH), chronic active EBV (CAEBV), or lymphoma.[17]
During the infection's acute phase, individuals generally have high levels of infective EBV in their oral/nasal secretions plus high blood levels of EBV, atypical lymphocytes, CD8 T cells, and memory B cells (up to 50% of the latter cells are EBV+). The tonsils and cervical lymph nodes in these cases are hyperplasic and contain mixtures of normal-appearing lymphocytes, activated lymphocytes, plasma cells, and Reed–Sternberg-like cells.[14] Many of these normal-appearing and activated B cells and a small percentage of the tissue's T and NK cells are EBV+ with the virus being mostly in its lytic cycle rather than latent phases.[1] The diagnosis of mild IM cases is often overlooked or made based on clinical and routine laboratory findings. These cases as well as asymptomatic and more severe cases of EBV infection are diagnosed definitively as EBV-associated by finding during the initial infection period the Epstein–Barr virus, IgM antibody to EBV viral-capsid antigen (VCA-IgM), IgG antibody to VCA (IgG-VCA), and IgG antibody to EBV viral- capsid antigen (EBNA1-IgG) in the blood[10] and/or finding EBV in the oral/nasal secretions.[14] There are no controlled studies on the treatment of uncomplicated EBV+ IM. Short-term courses of corticosteroid drugs are often prescribed for patients afflicted with airways obstruction, autoimmune reactions (e.g. autoimmune anemia or thrombocytopenia), or other complications of the disease.[17] Treatment of these and the severest IM cases generally use regimens directed at the specific features of each type of complication.[10]
### Epstein–Barr virus-related hemophagocytic lymphohistiocytosis[edit]
Main article: Hemophagocytic lymphohistiocytosis
Main article: Macrophage activation syndrome
Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterized by a systemic inflammatory or, in extreme cases, overwhelming cytokine storm condition. It is due to the pathological proliferation and activation of benign histiocytes, macrophages, and lymphocytes along with the excessive release of proinflammatory cytokines by these cells.[1] HLH has two distinct types. Primary HLH (also termed genetic or familial HLH) is caused by loss of function (i.e. inactivating) mutations in genes that cytotoxic T and/or NK cells use to kill targeted cells such as those infected with EBV. These include mutations in the UNC13D, STX11, RAB27A, STXBP2, and LYST genes that encode elements needed for these cells to discharge toxic proteins into targeted cells; mutations in the PFP gene that encodes one of these toxic protein, perforin 1; and mutations in the SH2D1A, BIRC4, ITK1, CD27, and MAGT1 genes that encode proteins required for the development, survival, and/or other cell-killing functions of ctyotoxic T and/or NK cells.[18]
Secondary HLH is associated with and thought to be promoted by malignant and non-malignant diseases that, like primary HLH, also weaken the immune system's ability to attack EBV-infected cells. Malignant disorders associated with secondary HLH include T-cell lymphoma, B-cell lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, and the myelodysplastic syndrome. Non-malignant disorders associated with secondary HLH include: autoimmune disorders such as juvenile idiopathic arthritis, juvenile Kawasaki disease, systemic lupus erythematosus, the juvenile onset and adult onset forms of Still's disease, and rheumatoid arthritis;[18] immunodeficiency disorders such as severe combined immunodeficiency, DiGeorge syndrome, Wiskott–Aldrich syndrome, ataxia telangiectasia, and dyskeratosis congenita);[19] and infections caused by EBV, cytomegalovirus, HIV/AIDS, bacteria, protozoa, and fungi. Secondary HLH may also result from iatrogenic causes such as bone marrow or other organ transplantation; chemotherapy; or therapy with immunosuppressing agents;[20] About 33% of all HLH cases, ~75% of Asian HLH cases, and nearly 100% of HLH cases caused by mutations in SH2D1A (see X-linked lymphoproliferatgive disease type 1) are associated with, and thought triggered or promoted by, EBV infection. These cases are termed Epstein-Barr virus-positive hemophagocytic lympphohistiocytosis (EBV+ HLH).[21] In EBV+ HLH, the virus may be found in B cells but mainly infects NK and T cells, including cytotoxic T cells. The virus induces defects in the ability of cytotoxic T cells to kill other EBV-infected cells and causes them to overproduce pro-inflammatory cytokines. These cytokines stimulate histiocyte and macrophage development, activation, proliferation, and cytokine production.[1] The excessive release of these cytokines (e.g. tumor necrosis factor-α, interferon-γ, Interleukin 1 beta, interleukin 18, and CXCL9) causes a systemic and often overwhelming inflammatory condition.[21]
Primary HLH is most often seen in Asians <4 years of age while secondary HLH is most often seen in older children and adults of various races.[1] Typically, the disorder presents with fever, decreased numbers of circulating white blood cells and/or platelets, enlarged liver and/or spleen, clinical evidence of hepatitis, and/or central nervous system disturbances[21] such as irritability, decreased levels of consciousness, seizures, meningitis (i.e. neck stiffness, photophobia, and headache), impaired cranial nerve function, hemiplegia, ataxia (i.e. poor coordination of complex muscle movements), and reduced muscle tone.[18] Laboratory studies show abnormal liver function tests, reduced levels of blood fibrinogen, impaired blood clotting, and high levels of blood ferritin, triglycerides, soluble interleukin-2 receptor, and, in EBV+ HLH cases, circulating EBV. In the latter cases, histological examination of lymphatic, bone marrow, liver, neuronal, and other involved tissues show infiltrations of small EBV+ T cells, scattered small bystander EBV+ B cells, reactive histiocytes, reactive macrophages, and, in ~70% of cases, hemophagocytosis, i.e. ingestion of erythrocytes, leukocytes, platelets, and/or their precursor cells by histiocytes and macrophages. (Evidence of hemophagocytosis is not critical for the diagnosis of HLH.) The EBV in infected lymphocytes is in its lytic cycle rather than any latent phase.[1] Criteria consistent with the diagnosis of HLH, as developed by the Histiocytic Society (2004), include finding 5 of the 8 following signs or symptoms: fever ≥38.5 °C; splenomegaly; low blood levels of any 2 of the following, hemoglobin (<10 mg/L), platelets (<100,000/μL), or neutrophils <1,000/μl; either one or both of the following, blood fasting triglyceride levels >265 mg/dL or fibrinogen levels <150 mg/dL; hemophagocytosis in lymphoid tissue; low or absent NK cell activity as tested in vitro on blood cell isolates; elevated blood levels of ferritin; and elevated blood levels or the soluble IL-2 receptor.[21] The finding of EBV in T cells of blood or involved tissues is required to diagnose the EBV-associatec disease.[1]
Prior to 1994, the treatments used for HLH were generally unsuccessful with average response rates to therapeutic interventions of ~10% and median survival times of ~12 month. In 1994, the Histiocytic Society established a drug regimen of dexamethasone \+ etoposide that increased the response rate to 70%. This regimen is currently recommended, particularly for primary HLH in young children, as induction therapy for EBV+ HLH except in patients with the macrophage activation syndrome where pulse methylprednisolone is the preferred treatment. Response rates are somewhat higher in young children than adults and in primary rather than secondary disease. Following inductive therapy, allogenic hematopoietic stem cell transplantation preceded by a reduced intensity conditioning regimen has been employed selectively, particularly in cases with primary HLH, with early results reporting some success.[22] The management of EBV+ HLH has been less successful than that for other causes of secondary HLH.[10] Novel approaches to HLH particularly in cases of refractory or recurrent disease include the use of antithymocyte globulin, the DEP regimen (i.e. liposomal doxorubicin, etoposide, methylprednisolone), an anti-interferon gamma monoclonal antibody,[22] and, particularly in patients with EBV+-HLH, rituximab.[10]
### Chronic active Epstein–Barr virus infection[edit]
Main article: Chronic active EBV infection
Chronic active Epstein–Barr virus infection (CAEBV) (also termed chronic active EBV infection of T and NK cells, systemic form) is a rare LPD[1] of children and, less often, adults.[23] CAEBV presents as severe, persistent form of infectious mononucleosis (IM) or a severe LPD disorder that follows months to years after a symptomatic (i.e. IM) or asymptomatic EBV infection. Characteristic findings that are also diagnostic criteria for the disorder are: 1) symptoms similar to those in infectious mononucleosis but persist for >3 months; 2) high blood levels of EBV DNA (i.e. >25 viral copies per mg of total DNA); 3) histologic evidence of organ disease; 4) presence of EBV RNA (e.g. an EBER) in an afflicted organ or tissue; and 5) occurrence of these findings in individuals who do not have a known immunodeficiency, malignancy, or autoimmune disorder. Other symptoms of CAEBV include persistent or intermittent fever, enlargement of lymph nodes, spleen, and/or liver, severe mosquito bite allergy, rashes, herpes virus-like skin blistering, diarrhea, and uveitis. The disorder may take a protracted course without progression over several years or a fulminant course with life-threatening complications such as Hemophagocytosis (i.e. ingestion of blodd cells by histiocytes), myocarditis, liver failure, interstitial pneumonia, or rupture of the intestines.[14] CAEBV can progress to a malignant type of EBV+ T-cell LPD such as aggressive NK cell leukemia, NK/T cell leukemia, or peripheral T cell lymphoma.[24]
The disorder may involve EBV+ T, NK, or, rarely, B cells. In EBV+ T and NK cell-associated disease, the tissues affected by CAEBV usually exhibit an histology that is not suggestive of a malignancy: lymph nodes have areas of hyperplasia, focal necrosis, and small granulomas; spleen shows atrophy of white pulp with congested red pulp; liver contains infiltrations of small lymphocytes around portal vasculature and sinuses; and lung and heart have findings typical of interstitial pneumonitis and viral myocarditis, respectively. Erythrophagocytosis (i.e. ingestion of red blood cells by histiocytes) often occurs in the bone marrow, spleen, and/or liver. The principal EBV+ cells in these tissues are T cells in ~59%, both T- and NK cells in ~40%,[14] and B cells in ~2% of cases. The involved lymphoid tissues in EBV+ B cell cases contain proliferating Immunoblasts (i.e. activated B cells), plasma cells, and Reed-Sternberg-lide cells.[1] The EBV+ cells in CAEB express primarily LMP1, LMP2, and EBNA1 viral proteins and EBER microRNAs,[14] suggesting that the virus is in its latency II phase.[1] The mechanism underlying the development of CAEBV is unclear. However, patients with CAEBV have a hyper-inflammatory condition with elevated blood levels of the same cytokines (i.e. IL-1β, IL-10, and IFNγ) seen in hemophagocytic lymphohystiocytosis. Furthermore, the disease has a strong racial preferences for Eastern Asians. These associations suggest that there are strong genetic predispositions involved in the disease's development and that this development is driven by T- and/or NK cell production of inflammatory cytokines.[14]
Initially, CAEBV may assume a relatively indolent course with exacerbations and recoveries. However, the disease almost invariably develops lethal complications such as single or multiple organ failures. Current recommendations based on studies in Japan suggest that patients diagnosed with CAEBV be treated early in their disease with an intensive 3 step sequential regimen: 1) immunotherapy (prednisolone, cyclosporine A, and etoposide; 2) cytoreduction (vincristine, cyclophosphamide, pirarubicin, and prednisolone or, alternatively, prednisolone and cyclosporine A); and 3) reconstruction: allogeneic hematopoietic stem cell transplant preceded by reduced intensity drug conditioning (i.e. etoposide and cytosine arabinoside followed by fludarabine, melphalan, anti-thymocyte globulin, methylprednisolone, and etoposide). Patients receiving this regimen obtained unusually high 3 year event-free and overall survival rates of >87%. Further studies are required to determine how long these event-free and overall survival rates endure.[25]
#### Severe mosquito bite allergy[edit]
Main article: Mosquito bite allergies
Severe mosquito bite allergy (SMBA) is a rare disorder which occurs mainly in young East Asians (median age 6.7 years). In most cases, it is a manifestation of CAEBV infection of the EBV+ NK cell type: ~33% of all individuals with CAEBV develop this allergy. SMBA has also been reported to occur in rare cases of EBV positive Hodgkin disease,[26] hydroa vacciniforme, aggressive NK‐cell leukemia (also termed aggressive NK-cell leukemia/lymphoma), and extranodal NK/T-cell lymphoma, nasal type,[27] as well as in EBV negative LPD such as chronic lymphocytic leukemia and mantle cell lymphoma.[26] EBV+ SMBA is a hypersensitivity reaction. In CAEV, the best studied or the predispositions to the disorder, SMBA is characterized by the development of skin redness, swelling, ulcers, necrosis and/or scarring at the site of a mosquito bite. This is often accompanied by fever and malaise;[14] enlarged lymph nodes, liver, and/or spleen; liver dysfunction; hematuria; and proteinuria.[26] Afflicted individuals have increased blood levels of immunoglobulin E (which plays an essential role in the development of type I hypersensitivity reactions of the skin and other tissues) and EBV+ NK cells.[1] In severer cases, the disorder is complicated by hemophagocytosis, NK/T-cell lymphoma, or aggressive NK cell leukemia.[14] Diagnostically, the skin lesions show infiltrating NK cells in the epidermis and subcutaneous tissue with a small fraction of these cells being EBV+ with the virus in its latency II phase. A very high density of EBV+ NK cells in these lesions suggests the disorder has progressed to NK/T cell lymphoma or NK cell leukemia.[1] While the disorder's etiology is unclear, it is thought that the mosquito salivary gland allergenic proteins trigger reactivation of EBV in latently infected NK cells. Upon reactivation, EBV genes such as LMP1 express products that induce immortalization, proliferation, and in some cases malignancy of the EBV reactivated NK cells.[26] The best treatment for SMBA remains unclear. Mild and clearly uncomplicated cases can be treated conservatively focusing on obtaining relief of symptoms such as skin irritation, fever, and malaise.[28] However, cases with evidence of significant complications of CAEFV such as the development of hemophagocytosis, NK/T cell lymphoma, or aggressive NK cell lymphoma, support the use of the chemotherapeutic regimens directed at these complications. Cases of EBV+ SMBA associated with clear evidence of concurrent aggressive CAEBV have been treated with relative success by the 3 step regimen used to treat CAEBV.[25] Rare cases of SMBA have been reported to occur in individuals who have no apparent predisposing disease but later develop CAEBV.[27][28] Such cases require careful evaluation and follow-up for development of a predisposing disorder.[28]
#### Hydroa vacciniforme-like lymphoproliferative disease[edit]
Main article: Hydroa vacciniforme
Hydroa vacciniforme is a rare photodermatitis reaction in which sunlight causes itchy skin papules and vesicles that develop crusts and eventually become scarred tissue. The lesions occur primarily on the sun-exposed skin of the face and back of the hand. It is an EBV+ disorder in which most cases develop in children, follow a waxing and waning course, and resolve in early adulthood. However, the disorder can occur in adults. Furthermore, the disease in children or adults may progress to cause severe, extensive, and disfiguring skin lesions unrelated to sunlight exposure, facial edema, and systemic manifestations such as fever, weight loss, and enlargements of lymph nodes, liver, and/or spleen. These cases may progress to an EBV+ LPD such as T cell lymphoma, T cell leukemia, B cell lymphoma, or B cell leukemia.[23] The milder and more aggressive forms of hydroa vacciniforme were initially termed classic hydroa vacciniforme and hydroa vacciniforme-like lymphoma, respectively, but extensive overlap between the two disease types lead the 2016 World Health Organization to reclassify them into a single disorder termed Hydroa vacciniforme-like lymphoproliferative disease and to be a subcategory of CAEBV. Histological examination of the skin lesions reveals infiltrating lymphocytes most of which are T cells and a minority of which are NK- or B- cells.[23] In the skin lesions, EBV occurs primarily in the T cells[1] and to a lesser extent NK cells.[14] Marker studies indicate that the EBV in these cells is in latency phase II.[1]
Treatment of the non-aggressive cases of hydroa vaccinforme-like lymphoproliferative disease follow standard dermatological practices for non-malignant diseases. For malignant cases of the disease, Immunotherapeutic drugs prednisone, interferon-α, chloroquine, and thalidomide) have given temporary remissions and improvements; standard chemotherapy and radiotherapy regimens used to treat lymphoma and leukemia have produced only transient benefits while often causing unacceptable toxicities.[23] Cases of EBV+ hydroa vacciniforme-like lymphoproliferative disease associated with clear evidence of concurrent CAEBV have been treated with relative success by the 3 step regimen used to treat CAEBV.[25]
### Epstein–Barr virus-positive mucocutaneous ulcer[edit]
Main article: Mouth ulcer § Epstein-Barr virus-positive mucocutaneous ulcer
EBV+ mucocutaneous ulcer is a rare lymphoproliferative disorder in which infiltrating B cells cause solitary, well-circumscribed ulcers in mucous membranes and skin.[1] The disorder afflicts individuals who have poor immune function because of old age, immunosuppressant diseases (e.g. HIV/AIDS), immunosuppressive drug therapy, or allogenic hematopoietic stem cell transplantation. Immunosuppressive drugs associated with the development of these ulcers include methotrexate (the most often cited drug causing the disease), cyclosporin A, azathioprine, mycophenolate, TNF inhibitors, tacrolimus, and topical steroids. It is thought that the reduce efficacy of immune surveillance associated with these predisposing conditions or treatments maintain EBV in a dormant state systemically but not where EBV+ B cells are prevalent, i.e. in afflicted mucous membranes and skin. Consequently, the EBV+ cells at these sites proliferate and destroy tissue to create ulcerating lesions.[23]
Persons developing these ulcers are usually elderly. Their ulcers are typically isolated, occur in the oral mucosa and less commonly in skin or gastrointestinal tract mucosa. Besides pain at the ulcer site and local tissue destruction (which may be severe), individuals with EBV+ mucocutaneous ulcer are symptomless and lack lymphadenopathy (i.e. enlarged and painful lymph nodes), involvement in other tissues, or B symptoms. However, ulcers in the gastrointestinal tract may present with a variety of abdominal symptoms including acute emergency perforations. Unlike most other forms of EBV+LPD, EBV-associated mucocutantious ulcers are generally not associated with detectable blood levels of EBV.[23] Microscopically, the ulcers consist of lymphocytes, including EBV+ B cells, sometimes a scattering of other EBV+ lymphoid cell types, and histiocytes, plasma cells, eosinophils, and scattered large immunoblasts which may closely resemble but are not the Reed–Sternberg cells seen in Hodgkin lymphoma.[14] These Reed-Sternberg–like cells are EBV+ B cells that express the tumor marker cell surface membrane protein, CD30, the B cell surface membrane marker, CD20,[23] and the proteins typical of the EBV replication cycle latency II or III phase.[1]
In elderly individuals with no other cause for immunosuppression, EBV+ mucocutaneous disease may exhibit a relapsing and remitting course with their ulcers worsening but then regressing spontaneously.[23] Persistent and/or severely symptomatic cases have had excellent responses to rituximab, a commercial monoclonal antibody directed against the CD20 protein present on B cells.[14] Individuals developing these ulcers as a consequence of immunosuppressive therapy for other diseases generally have a remission after the dosages of the drugs used in their immunosuppressive treatment regimens are reduced. Most of these patients do not experience a relapse.[23]
## EBV+ B cell lymphoproliferative diseases[edit]
After its initial entry into B cells, the Epstein–Barr virus infects other B cells and in doing so may or may not cause a symptomatic disease viz., infectious mononucleosis. In either case, the virus soon switches to its dormant, viral latency 0 phase within memory B cells and the infected individual becomes an asymptomatic, lifelong EBV carrier. At any time thereafter, however, the virus may reactivate, enter either its lytic cycle, latency phase II, or latency phase III; spread to other lymphoid cells, and drive its infected cells to proliferate excessively, survive abnormally, and establish an EBV+ LPD.[1]
### Epstein–Barr virus-positive Burkitt lymphoma[edit]
Main article: Burkitt's lymphoma
Burkitt lymphoma occurs in three forms. Epidemic Burkitt lymphoma (eBL) is common in Africa, the Middle East, Brazil, Papua New Guinea, and other areas where malaria is endemic. It usually presents in children 4–7 years old and in almost all cases is associated with EBV infection.[29] Sporadic Burkitt lymphoma (sBL) is rare. It occurs in children and, less commonly, older (>60 years) adults.[14] It is found primarily in Northern and Eastern Europe, East Asia, and North America.[30] There are ~1,200 cases/year in the USA.[29] Only 10–15% of sBL cases are associated with EBV infection.[31] The immunodeficiency-related form of Burkitt lymphoma (iBL) strikes 30–40% of individuals with HIV-induced AIDS[14] and rare cases of patients who received a bone marrow or other organ transplant; in the latter cases, individuals have almost always received intensive chemotherapy and therefore are immunodeficient.[30] About 30% of iBL cases are infected with EBV.[32]
eBL commonly presents with a jaw mass; periorbital swelling due to an orbital tumor; or an abdominal mass caused by a tumor in the retroperitoneum, kidney, or ovary. Less commonly, it present as a sudden onset of paraplegia or urinary incontinence due to tumor infiltration into neural tissue. sBL commonly presents with abdominal pain, nausea, vomiting, and/or gastrointestinal bleeding caused by the growth of an abdominal tumor; a head or neck tumor in lymph nodes, tonsils, nose, sinuses, and/or oropharynx); or extensive bone marrow infiltrations by malignant tumor cells.[30] iBL commonly presents with fever, other constitutional symptoms, and tumors in the gastrointestinal tract, bone marrow, liver, lung, and central nervous system.[33] Histologic examination of BL-involved tissues shows infiltrations by a uniform population of rapidly proliferating (i.e. mitotic index approaching 100%) and rapidly turning over (i.e. cells not only rapidly proliferate but also rapidly die due to apoptosis) lymphocytes punctuated by intermittent clear spaces where macrophagess containing ingested dead cells give the tissues the impression of a "starry sky" pattern. The lymphocytes are primarily B cells (e.g., express CD20 and CD10 markers) with rare T cells evident only in the background.[30] The B cells are derived mostly from germinal center B cells, contain EBV in latency I phase, and express high levels of EBNA1 and EBER viral products. Some cases also express other EBNA and the LMP2A products.[1] EBNA1 and EBER proteins may contribute to the development and/or progression of BL by inhibiting the death by apoptosis of the cells they infect while the product of LMP2A may activate the infected cell's PI3K cell signaling pathway thereby stimulating this cell's proliferation.[citation needed]
The malignant B cells in all three forms of BL commonly have acquired chromosomal translocations involving their MYC gene. MYC is a proto-oncogene (i.e. a cancer-causing gene if appropriately mutated or overexpressed) located on the long ("q") arm of human chromosome 8 at position 24 (i.e. at 8q24). In ~90% of BL cases, MYC is translocated to the IGH (i.e. Immunoglobulin heavy chain) gene locus at position 14q32, the IGK (i.e. immunoglobulin kappa light chain) gene at position 2p12 ("p" stands for short chromosome arm), or the IGL (i.e. immunoglobulin lambda light chain) gene at position 22q11. These translocations bring MYC under the transcriptional control of these antibody-forming loci and thereby cause the MYC product, Myc to be overexpressed and continuously driving the infected cell to proliferate. Mutations in other genes of the infected cell may promote its malignancy, e.g. ~30% of BL cases harbor B cell P53 gene mutations which may promote cell survival.[14] These alternate, potentially EBV-independent routes to malignancy and the fact that some BL cases do not involve EBV allow that many cases of EBV+ BL are not caused and/or promoted by EBV: the ubiquitous virus is the likely cause of almost all cases of eBL but be an innocent passenger virus in many cases of sBL and iBL.[1]
Patients with any of the three forms of BL (with or without an association with EBV) are treated with multiple drug chemotherapy regimens. While past studies found much better results in children than adults using this approach, recent studies report that more aggressive chemotherapy regimens that include the intrathecal administration of drugs give better results. The COCOX-M-IVAC regimen (systemic cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine plus intrathecal methotrexate and cytarabine) give event-free 2 year response rates of >90% in both children and adults. Addition of rituximab, a monoclonal antibody against the CD20 antigen expressed on B cells, may be added to this or other multiple drug regimens. Autologous stem cell bone marrow transplantation has not improved the results of these regiments. Treatment of HIV-associated iBL is similar to, and has success rates comparable, to non-HIV BL, particularly when coupled with treatment directed at HIV although adults >40 years old have had poorer responses to these regiments. Cases refractory to these regimens have a poor prognosis with average overall 3 year survival rates of ~7%.[29]
### Epstein–Barr virus-positive lymphomatoid granulomatosis[edit]
Main article: Lymphomatoid granulomatosis
EBV+ lymphomatoid granulomatosis (EBV+ LG, also termed lymphomatoid granulomatosis [LG]) is a rare disease that involves malignant B cells and reactive, non-malignant T cells; it is almost always EBV+.[1] This LPD occurs primarily in middle aged males (male:female ratio 2:1). EBV+ LG usually (~90% of cases) presents as a lung disorder with coughing, hemoptysis, shortness of breath, and chest X-rays showing multiple nodular lesions at the base of both lungs. It may also evidence signs and symptoms caused by nodular or infiltrative lesions in the skin, central nervous system,[34] kidney, liver,[1] and/or peripheral nervous system,[35] At presentation the disease usually does not involve lymph nodes.[1] In rare cases it may not even involve the lung.[36] The lesions in EBV+ LG consist of occasional large, atypical B cells[34] located in a background of numerous reactive CD4+ Helper T cells, plasma cells, macrophages, and variable numbers of large atypical lymphoid cells which resemble immunoblasts, plasmablasts, or Reed–Sternberg cells. The lesions often center around and evidence destruction of small blood vessels but, paradoxically, do not contain well‑formed granulomas.[36] Only the lymphoid B cells in the lesions are EBV+; these cells express LMP1 and EBNA2 viral proteins and therefore carry EBV in its latency III phase.[1]
Individuals with the disease may be immune deficient due to subtle reductions in their immune function[1] or, based on individual case reports, immunodeficiency diseases such as HIV/AIDS, common variable immunodeficiency, X-linked agammaglobulinemia, hypogammaglobulinemia, sarcoidosis,[37] methotrexate-treated rheumatoid arthritis, or the Wiskott–Aldrich syndrome.[36] They may also have, again based on case reports, a history of inflammatory/autoimmune diseases such as chronic hepatitis, ulcerative colitis, retroperitoneal fibrosis, or primary biliary cholangitis.[37] EBV+ LG may progress to or become complicated by the non-malignant skin disease, lymphomatoid papulosis, or a second lymphoid malignancy such as Hodgkin lymphoma, mycosis fungoides, CD30+ anaplastic large cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, or diffuse large B cell lymphoma.[38] EBV+ LG appears in part due to the virus causing its infected B cell to release chemokines which attract, and thereby stimulate T cells to injure tissues, particularly blood vessels. Impaired host immune function and failure of infected cells to express viral proteins recognized by cytotoxic T cells allows EBV+ B cells to evade the immune system and proliferate.[36]
LG presents as one of three grades based on the histology of biopsied tissues: grade I (<5 EBV+ cells per high power microscopic field (hpf), no atypical cells/hpf, and minimal necrosis); grade II (5–20 EBV+ cells/hpf, occasional atypical cells/hpf, and moderate necrosis); and grade III (>20 EBV+ cells/hpf, predominance of atypical cells/hpf, and extensive necrosis). Grade I disease may not need therapy and, in rare cases, remits spontaneously.[36] Grade II and severe grade I disease is treated with immune regimens that include various interferons[36] and/or rituximab, a monoclonal antibody against the B cell protein, CD20.[34] Grade III and severe grade II disease are treated with either high dose glucocorticoids; chemotherapy regimens such as CHOP, ICE, or Hyper-CVAD; or combinations of these treatments. However, the efficacy of interferon-α and rituximab in EBV+G is disputed.[34]) While EBV+ LG often responds to these treatments, there are no controlled clinical trials proving their long-term therapeutic value.[36] Medium survival times for all cases of the disease are ~4 years with many cases progressing to other lymphoid malignancies that shorten survival times.[36]
### Epstein–Barr virus-positive Hodgkin lymphoma[edit]
Main article: Hodgkin lymphoma
Hodgkin lymphoma (HL) falls into two histologic forms, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (cHL) with cHL being divided into nodular sclerosis (NSHD), mixed cellularity (MCHD), lymphocyte rich (LRHD), and lymphocyte depleted (LDHD) subtypes. EBV is found in 30% to 50% of HL cases, but occurs in ~90% of NSHD and MCHD but ≤10% of LRHD, LPHD, or NLPHD cases. HL involves the infiltration of T cells, B cells, macrophages, eosinophils, fibroblasts, and Reed–Sternberg cells (HRS cells, also termed Hodgkin Reed-Sternberg cells) into lymphoid and other tissues. HRS cells are large mono- or poly-nuclear cells which: 1) derive from lymph node and/or spleen germinal center B cells; 2) may contain EBV and viral products indicative of stage II latency; and 3) are the only malignant cells in, and the mediators of, HD.[39] EBV in HRS cells are thought to play a role in the pathogenesis (i.e. development) of EBV+ HL. These cells express uniquely high levels of the virus's LMP1 gene. This gene product protein, LMP1, mimics activated human TNF receptors (e.g. CD40, CD40, and RANK) in continuously stimulating the NF-κB, PI3K and JAK-STAT signaling pathways which promote cell proliferation, survival, and production of cytokines that may suppress the EBV's lytic cycle to maintain the HRS cells viability.[39] HRS cells also express the virus's LMP2A gene protein product which mimics the human BCR gene product) in promoting the survival of its parent cells.[1] And, EBV, by undefined mechanisms, causes crippling mutations in the HRS cell's rearranged immunoglobulin G genes to prevent them from expressing immunoglobulins and inducing them to secrete cytokines which recruit the other cited cell types into the EBV+HL's pathological infiltrates. This helps create a local environment conducive for HRS cells to evade the immune system and proliferate.[39]
EBV+ HL is more prevalent in young children and young adults but can occur in those over 80 years old, perhaps because of old age-related deterioration in immune system function, infectious diseases, or malnutrition.[1] The incidence of EBV+ HD's in individuals with HIV/AIDS is also high, ~10-fold greater than the general population, but the causes for this is unclear.[39] The presentation of EBV+ HL is similar to that of EBV-HL, e.g. fever, night sweats, weight loss in the setting of swollen lymph nodes, and/or evidence of tumor invasion of other tissues. Treatment of the EBV+ HD is also similar to EBV- HD and offers cure rates approaching 90%,[14] although some population based studies have found a higher incidence of relatively adverse outcomes in older individuals with EBV+ HL.[1]
### Epstein–Barr virus-positive diffuse large B cell lymphoma, not otherwise specified[edit]
Main article: Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the second most common type of lymphoma. It occurs primarily in elderly adults, far less frequency in younger adults, and rarely in children. Elderly adults present with B symptoms (i.e. fever, night sweats, and weight loss), swollen lymph nodes, and symptoms due to malignant cell infiltrations into the upper gastrointestinal tract, lungs, upper airways, and/or other organs. Younger individuals present with swollen lymph nodes but frequently do not have class B symptoms or involvement of extra-nodal tissues. It is a more aggressive disease in the elderly.[14] Histologic features of DLBCL can be divided into three patterns based on the cell types in tissue infiltrates; the anplastic variant (~3% of cases) exhibits prominent Reed–Sternberg-like cells[40] embedded in a background of histiocytes and lymphocytes;[14] the immunoblastic variant (8–10% of cases) has 90% immunoblasts; and the centroblastic variant (80% of cases) is dominated by centroblasts.[40] These histological features are typically accompanied by the invasion and destruction (i.e. necrosis) of small blood vessels. An alternative classification is based on the disease's cell of origin: germinal center B cell DLBCL (GCB-DLBCL) and activated B cell DLBCL (ABC-DLBCL).[14] Uncommonly, DLBCL occurs by what is known as a Richter transformation of chronic lymphocytic leukemia (CLL) to an extremely aggressive form of DLBCL. Many of these transformations develop in EBV-associated CLL cases (~10–15% of all CLL cases are EBV-associated).[41]
About 10–15% percent of DLBCL cases are EBV+. These cases, termed Epstein–Barr virus-positive (EBV+) diffuse large B cell lymphoma, not otherwise specified (EBV+ DLBCL), occur predominantly in East Asia and Mexico and less commonly in Europe and the USA. EBV+ DLBCL is distinguished from DLBCL (often termed diffuse large B-cell lymphoma, not otherwise specified, i.e. DLBCL, NOS) in that virtually all the large B cells in the tissue infiltrates of the EBV+ disease type express EBV genes characteristic of the virus's latency III (common in the elderly) or II (common in younger patients) phase.[31] These large B cells in EBV+ DLBCL are centroblastic (i.e. activated) B-cells[8] that express EBERs,[14] LMP1, EBNA1, EBNA2, and other viral proteins;[1] in >50% of cases, they also express classic B cell antigenic proteins such as CD20, BCL6, and CD15. The viral proteins may be responsible for activating their infected cells' NF-κB, STAT/JAK, NOD-like receptor, and Toll-like receptor cell signaling pathways which may act to promote the proliferation and survival of the infected cells.[1]
EBV+ DLBCL commonly occurs in immune-deficient individuals. It is thought to arise in the elderly because of their immunosenescence as manifested by an age-related decline in the specific types of CD4+ and CD8+ lymphocytes that function to suppress the growth of EBV+ cells.[1] EBV+ DLBCL also occurs in individuals who are overtly immunosuppressed due to HIV/AIDS (~33% of HIV/AIDS cases are EBV+) or anti-rejection drug therapy following solid organ transplantation (30% to 70% or these cases are EBV+).[39] Similarly, the Richter transformation of EBV+ CLL to EBV+ DLBCL occurs primarily in CLL cases treated with immunosuppressant drugs and therefore appears due in part to immunosuppression-related reactivation of the latent EBV infecting these CLL cells.[41] Currant treatments for EBV+ and EBV- DLBCL use either R-CHOP (rituximab, chimeric anti-CD20 monoclonal antibody, cyclophosphamide, doxorubicin, vincristine, and prednisone or R-EPOCH [rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). Responses to these regimens are poor in EBV+ DLBCL (median survival 2 years),[42] particularly in CLL-transformed EBV+ DLBCL (median survival 4 months).[43]
#### Epstein–Barr virus-associated diffuse large B cell lymphoma associated with chronic inflammation[edit]
Main article: Diffuse large B-cell lymphoma associated with chronic inflammation
Diffuse large cell lymphoma associated with chronic inflammation (DLBCL-CI) is an extremely rare EBV-positive DLBCL[1] that arises as a mass in areas of longstanding inflammation, usually body cavities or narrow spaces.[44] Almost all of the reported cases of DLBCL involve pyothorax-associated lymphoma (PAL). PAL occurs years after a pneumothorax is medically induced in order to collapse a lobe or entire lung around a cavity[44] or to treat pleurisy (inflammation of the pleural cavity)[45] caused by an otherwise uncontrollable condition, almost always pulmonary tuberculosis. Reports on it are primarily in Japanese elderly males. Far less commonly, DLBCL-CI occurs in association with other chronic inflammation conditions such as osteomyelitis, medical insertion of a foreign body (intrauterine contraceptive devices, metallic implants, surgical mesh), skin ulcers, and venous ulcers. Signs and symptoms of DLBCL-CI reflect the destructive effects of the malignancy in the afflicted areas. The infiltrative lesions consist of diffuse large EBV+ B cells in latency III amidst a variety of benign, EBV-negative chronic inflammatory white blood cells. The EBV+ large B cells in these lesions often have reduced expression of the CD20 antigen and contain genetic abnormalities such as mutations in P53, overexpression of Myc, and deletion of TNFAIP3. These abnormalities differ form those in the EBV+ large B cells of ordinary DLBCL. Studies suggest that the disease arises as the result of the EBV-driven proliferation of large B cells in a confined anatomical space that segregates them from immune surveillance.[14] and/or of EBV-driven release of cytokines with anti-inflammatory activity (e.g. Interleukin 6 and Interleukin 10) that may also help the infected cells escape this surveillance.[1]
While DLBCL-CI is an aggressive malignancy, its treatment, particularly in localized disease, should include efforts to remove its underlying inflammatory causes.[46] For example, PAL is a particularly aggressive form of DLBCL-CI.[44] Nonetheless, surgical removal of the pleural tumor effectively treats the few cases in which it is localized and of low-grade.[14] More severe cases of PAL have been treated with chemotherapy regimens such as CHOP but overall 5 year survival rates with these regiments have been poor (~21%).[47] There are too few reports on the treatment of non-PAF forms of DLBCL-CI to make recommendations.
##### Fibrin-associated diffuse large B cell lymphoma[edit]
Main article: Fibrin-associated diffuse large B-cell lymphoma
Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is included as a provisional entry as a type of DLBCL-CI by the World Health Organization, 2016. It is an extremely rare disease that occurs in immunologically competent individuals.[1] It is due to the infiltration of large B cells into long-standing, avascular fibrin-based masses that develop in, on, or around long-standing hamartomas, pseudocysts, cardiac myxommas, prosthetic heart valves,[1] thrombus-laden in endovascular grafts, hematomas,[14] hydroceles, and prosthetic implants of the hip.[48] The infiltrations consist of sheets, ribbons, or clusters of proliferating large B cells within avascular tissue that are coated with or contain abundant fibrin plus a paucity or absence of other types of inflammatory cells.[48] The large B cells are infected with EBV in latency III and express this virus's EBER, EBNA2, and LMP-1 genes.[14] The infiltrations typically do not spread beyond these initial sites and there is no evidence of lymph node, spleen, or other tissue involvement: FA-DLBCL appears to be a non-malignant proliferation of EBV+ large B cells. Similar to DLBCL-CI, the development of FA-DLDCL may be due to localized immune suppression at its sites of origin. Unlike DLBCL-CI, however, the large B cells in FA-DLBCL appear unable to proliferate and survive long-term outside of the sequestered sites; consequently, the EBV+ cells tend to spread beyond these sequestered sits and FA-DKBCL does not appear to be a truly malignant disease.[14] The two disorders also have other differences: the histology of the involved tissues in FA-DLBCL and DLBCL-CI are dissimilar and the large EBV+ B cells in FA-DLBCL, unlike those in DLBCL-CI, do not overexpress the Myc gene and have relatively few karyotype chromosomal abnormalities.[48]
Patients with FA-DLBCL present with signs and symptoms reflecting the location of the infiltrative lesion. When these lesions occupy the heart (e.g. on myxommas or prosthetic valves) or vasculature (e.g. on thrombus-laden vascular grafts) the disease may present as a life-threatening cardiovascular symptoms, particularly strokes.. Outside of these cardiovascular complications, the disease typically takes an indolent course without spreading beyond its site of origin. Removal of the tissues along with any associated foreign implant is usually curative. Refractory or recurrent disease has been treated with the CHOP (± rituximab) with only limited success.[48]
### Epstein–Barr virus-positive human herpes virus 8-associated B cell lymphoproliferative disorders[edit]
Human herpes virus 8 (HHV8) is associated with four rare lymphoproliferative disorders: 1) a subset of diffuse large B cell lymphoma (DLBCL), b) large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease, c) primary effusion lymphoma, and 4) germinotropic lymphoproliferative disorder. The latter two forms of HHV8+ lymphoproliferatvive disorders have been associated in rare case reports with EBV infection.[49]
#### Primary effusion lymphoma[edit]
Main article: primary effusion lymphoma
Primary effusion lymphoma (PEL) is a HHV8+ B cell lymphoma presenting as an effusion (i.e. excess fluid) in the pleural cavity (see pleural effusion), peritoneal cavity (see peritoneal effusion), or pericardium (see pericardial effusion). These effusions are due to the infiltration of HHV8-infected B cells into the membrane tissues that line these spaces. Tumor masses are infrequent and generally occur late in the disease. PEL is an aggressive, rapidly proliferating lymphoma that commonly spreads to multiple organs adjacent to the involved membrane tissues. Diagnosis of the diseases requires evidence of HHV8 virus involvement by detecting the HHV8 viral protein, LANA-1, in the malignant B cells.[49] PEL occurs primarily in individuals who are immunodeficient due to HIV/AIDS infection or solid organ transplantation. EBV is found in the malignant HHV8+ B cells of ~70% of PEL patients. However, a role for EBV in the development of PEL is not supported since HHV8 appears to drive the development and progression of the disease.[1] Treatment of PEL with surgery, radiation, chemotherapy (e.g. CHOP or EPOCH drug regimens), antiviral agents, and/or experimental drugs (e.g. rituximab, bortezomib) have not given results that are sufficiently beneficial to make clear recommendations. PEL reportedly has a median overall survival time of 4.8 months and 1, 3, and 5 year overall survival rates of 30%, 18%, and 17%, respectively.[50]
#### Epstein–Barr virus-positive, human herpes virus-positive germinotropic lymphoproliferative disorder[edit]
Human herpes virus-positive germinotropic lymphoproliferative disorder (HHV+ GLPD) is an extremely rare disorder characterized by the localized swelling of lymph nodes due to the infiltration by plasmablasts (i.e. immature plasma cells). The disorder generally occurs in immune-competent individuals[51] although it has been reported to occur in HIV-positive individuals. In most cases, the involved lymph nodes have a normal architecture with clusters of plasmablasts that are not only HHV8+ but also EBV+ with EBV likely being in its latency I phase. In the few cases reported, the disorder has shown good to excellent responses to chemotherapy. However, too few cases have been reported to make therapy recommendations or to define the role, if any, of EBV in the disorder.[1]
### Epstein–Barr virus-positive plasmablastic lymphoma[edit]
Main article: Plasmablastic lymphoma
Plasmablastic lymphoma (PBL) is an uncommon lymphoma that occurs mostly in immune-deficient individuals, primarily those with HIV/AIDS. Indeed, it is an AIDS-defining clinical condition.[14] The disease can also occur in those who have had an organ transplantation or chemotherapy treatment or are presumed to have age-related immune senescence.[49] Chronic autoimmune or inflammatory diseases (e.g. rheumatoid arthritis, Graves' disease, Giant-cell arteritis, sarcoidosis, or severe psoriasis) may also underlie development of PBL.[52] The disease occurs in individuals (male:female ratio 4:1) of all ages. It presents as a tumor of the head, neck, oral cavity, sinuses or, less commonly, gastrointestinal tact, skin, or other tissues. Histologically, the tumors are classified as monomorphic PBL (consisting predominantly of immunoblastic cells) or plasmacytic PBL (consisting predominantly of cells with features of plasma cells at varying stages of development). While originating from B cells, these cells express plasma cell markers such as CD79a, IR4, BLIMP1, CD38, and CD138.[14] About 70% of PBL cases are EBV+, with most of the lymphoma cells expressing EBV genes indicating that this virus is in latency phase 0 or I.[1] The disease appears to develop and progress as a result of the actions of both the EPV and human immunodeficiency virus (i.e.HIV) and, particularly in EBV+ disease, to be associated with overexpression of the MYC gene in EBV+ cells. Overexpressed MYC protein is thought to drive the disease but the role of EPV in MYC gene overexpression as well as the development and/or progression of EBV+ PBL is not clear. The prognosis of patients with advanced stage PBL, which is a common presentation of the disease in patients with HIV/AIDS, is poor (media survival 6–7 months).[49] However, PBL patients with early stages of the disease and/or EBV+ disease have a much better survival rate.[14] Overall, patients with HIV+ PBL respond to CHOP or EPOCH chemotherapy regimens with early results for the EPOCH regimen achieving medium survival rates that extend beyond 1 year.[53]
### Epstein–Barr virus-associated plasma cell myeloma[edit]
Main article: Multiple myeloma § Epstein-Barr virus
Plasma cell myeloma (PCM, also termed multiple myeloma), is a common cancer in which malignant plasma cells infiltrate the bone marrow or form soft tissue masses termed plasmacytomas. Rarely, EBV may be associated with this disease, particularly in individuals with an Immunodeficiency (e.g. HIV/AIDS, history of organ transplantation) or chronic inflammation (e.g. rheumatoid arthritis).[54] EBV positivity is more common in the plasmacytoma rather than bone marrow infiltration form of PCM.[1] Tissues involved in EBV+ PCM typically show foci of EBV+ cells with the appearance of rapidly proliferating (e.g. high mitotic index) immature or poorly differentiated anplastic plasma cells.[1] The cells express products of EBV genes such as EBER[55] which suggest that EBV is in a restricted latency II phase.[1] Although derived from B cells, these cells express plasma cell rather than B cell markers. The role of EBV in the development and progression of EBV+ PCM is unknown.[14] EBER-positive patients with the localized plasmacytoma form of PCM are more likely to progress to the infiltrative (i.e. systemic) form of PCM compared to individuals with EBV- disease.[55] The disorder has been treated with surgical removal in cases with one or two isolated plasmacytoma masses, radiation to isolated plasmacytoma tumor masses, and systemic chemotherapy (e.g. a doxorubicin, dexamethasone, and thalidomide regimen). However, post-therapeutic recurrence of the disease is common.[55]
## EBV+ NK/T cell lymphoproliferative diseases[edit]
While EBV preferentially infects B cells, it may also infect other lymphocyte types viz., CD4+ T cells (i..e T helper cells), CD8+ cells (i.e. cytotoxic T cells), NK cells (i.e. natural killer cells). The mechanism by which EBV infects these other cell types is unknown but may be their direct movement from B cells that are infected with the virus.[1]
### Peripheral T-cell lymphomas[edit]
Peripheral T cell lymphomas (PTCL) are a group of NK-cell or T-cell malignancies that include extranodal NK/T cell lymphoma, nasal type, peripheral T cell lymphoma, not otherwise specified (PTL, NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase positive or negative anaplastic large-cell lymphoma (AKL+/− ALCL).[56] AKL+/− ALCL is rarely if ever associated with EBV and therefore not considered here.[57]
#### Extranodal NK/T cell lymphoma, nasal type[edit]
Main article: Extranodal NK/T cell lymphoma, nasal type
Extranodal NK/T cell lymphoma, nasal type (ENKTL), is a malignancy of NK or, less commonly, T cells that afflicts primarily Asians and the indigenous populations of Mexico, Central America, and South America. It is less common in Western countries of the northern hemisphere. The disease usually consists of malignant tumors in the nasal cavities, paranasal sinuses, palate, tonsils, nasopharynx, hypopharynx, and/or larynx or, in ~20% of cases, tumors in the skin, soft tissues, gastrointestinal tract, testes, and/or central nervous system. Afflicted individuals are usually middle aged and present with obvious tumors, hemoptysis, ulcerating skin nodules, obstructions in the upper airways, and/or obstructions/bleeding in the lower gastrointestinal tract, particularly the colon. Involvement of lymph nodes is uncommon and generally due to the tumors' spread from their primary sites.[1] About 70% of ENLTL cases are diagnosed as having cancer stage I or II disease (tumors localized to a single site or region of the body ) with the remainder having disseminated stage III or IV disease.[58] All stages of ENKTL involve destructive, ulcerating, and necrotic lesions. Histologically, these tumors are composed of small, medium-sized, or large malignant lymphoid cells often accompanied by a mixture of benign inflammatory cells. The malignant cells express markers characteristic of NK and/or T cells (e.g. CD2, CD56, CD38), granzyme B, perforin, TIA1, and, with respect to T cells which are commonly gamma delta T cells in type, T-cell receptor gamma and delta chains).[14] In nearly all cases, the lymphoma cells are EBER+, show a latency II pattern of EBV infection,[1] have several somatic gene mutations among a group of >35 mutations know to be recurrent in the disease, and overexpress other genes (e.g. P53, and/or PD-L1).[11] The genes most often mutated are GAK (25.9% of cases), beta-catenin (22.9%), TP53 (22.7%), and ECSIT (19.3%). These genes regulate cell growth and survival.[14] Other genes (e.g. JAK3, STAT3, and STAT5B ) that are mutated in far lower percentages of cases also regulate these potentially pro-malignant cell functions. However, the relationship of EBV infection to these gene changes and the relationship of these changes to the development of ENKTL are unclear.[14]
The diagnosis of ENKTL depends upon finding EBV and granzyme B in the disease's lymphoid tumor cells.[14] Treatment varies with grade. For cancer grade I and II localized diseases, the recommended treatment is radiation directed at the tumor lesions plus a chemotherapy regimen such as DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin). Reported overall long-term survival and progression-free survival rates in Japan for individuals treated with this regimen are 72% and 61%, respectively. For stage III and IV disease, a more aggressive treatment regimen is used, SMILE (dexamethasone, methotrexate, leucovorin, ifosamide, L-asparaginase, and etoposide followed, in patients with ≥2 risk factors, by allogeneic bone marrow stem cell transplantation); this regimen reportedly achieves complete response and 5 year survival rates of 87% and 73%, respectively. Reported complete response and 5 year survival rates for relapsed or refractory ENKTL treated with the SMILE regimen are 45% and 47%, respectively.[58] PD-L1 (programmed death-ligand 1) functions to suppress the proliferation of antigen-specific T cells and promote the survival of inflammation-suppressing T cells; it is over-expressed in >80% of ENKTL cases. Preparations of the monoclonal antibody directed against PD-L1 have given encouraging results in small clinical trials on patients with relapsed/refractory ENKTL. For example, pembrolizumab achieved clinical response in 8 of 15 patients and nivolumab in 2 of 3 patients with recurrent/refractory ENKTL. Pembrolizumab is now included as a treatment option for recurrent/refractory ENKTL by the National Comprehensive Cancer Network.[59]
#### Epstein–Barr virus-associated peripheral T cell lymphoma, not otherwise specified[edit]
Main article: T cell lymphoma
Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS), is an aggressive, heterogeneous group of T cell malignancies with features that do not fit the diagnostic criteria for other types of PTCL.[9] About 30–40% of all PTCL cases are classified as PTCL, NOS. This lymphoma commonly occurs in men (median age ~60 years) who present with advanced stage III or IV disease (~70% of cases) characterized by T cell infiltrations that cause prevalent lymph node swelling often accompanied by evidence of bone marrow, liver, spleen, and/or skin involvement.[60] These individuals usually have B symptoms (i.e. fever, night sweats, weight loss).[61] Involved tissues exhibit mature-appearing T cells that express CD4.[62] However, attempts to define diagnostic criteria for PTCL, NOS by histology and immunophenotyping have not translated into clinical practice.[63] Gene expression profiling has proven more useful for diagnosing the disease: gene abnormalities commonly associated with PTLC, NOS include various fusion rearrangements of the VAV1 or TBX21 genes and fusion rearrangements of the ITK gene with the SYK, FER, or ERBB4 genes. Two distinct profiles of gene overexpression have emerged from these studies: the malignant cells may overexpress GATA3, MYC, mTOR, and β-catenin genes or, alternatively, the TBX21, interferon-γ, and NF-κB genes. Individuals whose malignant cells express the GATA3 gene group have a poorer overall 5 year survival than those whose malignant cells express the TBX2 gene group.[60] As defined by the expression of EBER, ~30% of PTCL, NOS cases exhibit malignant T cells that are infected with EBV; in these cases, the virus is in its latency II phase. However, few of these cases evidence strong EBER expression in the malignant T cells. More often, EBER expression in this disease is limited to the small and large benign B cells the populate the background of the disease's lesions. Thus, the relationship of EBV to the development and progression of PTCL, NOS is unclear.[1]
There are no controlled studies on the treatment of this disease. Recommended treatments for advanced stage PTCL, NOS (regardless of EBV status) include intensive chemotherapy regimens, e.g. CHOP, as induction therapy possibly followed by autologous hematopoietic stem cell transplantation. These regimens have shown only limited results with 5 year overall survival rates <50% for chemotherapy alone. These survival rates may be improved in patients able to withstand follow-up bone marrow transplantation. Newer drug approaches using Pralatrexate, Romidepsin, Brentuximab vedotin, Belinostat, Bendamustine, lenalidomide, and alisertib have shown activity against CTCL, NOS and are being further studied in randomized trials for use in treating refractory and relapsed as well as initial disease.[60]
#### Angioimmunoblastic T cell lymphoma[edit]
Main article: angioimmunoblastic T-cell lymphoma
Angioimmunoblastic T cell lymphoma (ATIL) is a systemic malignancy of mature follicular B helper T cells (TFH cells).[1] ATIL is often manifested soon after individuals ingest antibiotics or have an infection or allergic reaction. The disease presents with generalized swelling of lymph nodes, enlarged liver and spleen, skin lesions (rash, or, less commonly, nodules, plaques, purpura, and urticarial), bone marrow involvement, and B symptoms of fever, weight loss, and night sweats. Individuals may also present with arthralgias, arthritis, pleural effusions, ascites, lung lesions, and neurological and gastrointestinal disturbances. Laboratory tests commonly reveal the presence of immune-mediated hemolytic anemia; elevated blood levels of eosinophils, gamma globulins, and lactic dehydrogenase; high erythrocyte sedimentation rates; and positive blood tests for autoantibodies such as rheumatoid factor, anti-nuclear antibody, and anti-smooth muscle antibody. Several of these clinical and laboratory features suggest that the afflicted individuals have an underlining abnormality in their immune system. Involved tissues exhibit vascular proliferation, small lymphoid cells clustered around venules in a background containing TFH cells, activated lymphocytes, follicular dendritic cells, epithelioid cells, plasma cells, and eosinophils. Only the TFH cells are malignant. The latter cells represent 5–30% of all cells in the disease's lesions, express TFH cell marker proteins (e.g. CD3, CD4, CD10, programmed cell death protein 1 (PD-1), and also express the B lymphocyte chemoattractant, chemokine (C-X-C motif) ligand 13 (i.e. CXCL13).[64] Virtually all cases exhibit a scattering of EBV+ B cells with the virus possibly being in a restricted latency II phase. The other cell types in these lesions, including the malignant TFH cells are EBV negative. The EBV+ B cells have numerous non-malignant crippling mutations, often proliferate excessively, and in some cases transform into EBV+ B cell lymphomas.[1] EBV may be involved in the development and/or transformation of these EBV+ B cells to lymphoma but the virus's role in this as well as ATIL is uncertain.
The diagnosis of AITL depends on demonstrating TFH cells expressing the appropriated markers, particularly CXCL13; the presence of EBV+ cells supports the diagnosis. The malignant TFH cells in AITL have mutations in their TET2, IDH2, and RHOA genes in 30–83% of cases whereas the malignant cells in PTCL, NOS exhibit these mutations in 17%, 0%, and 0% of cases, respectively. Mutations in TET2 are the most prevalent (48% to 83% of cases) in AITL and generally occur in advanced-stage disease. Further study may add the presence of these mutations, particularly TET2, to AITL's diagnostic criteria.[65] The prognosis of ATIL has been poor. As rated by the International Prognostic Index (more severe disease with increasing score), 14% of AITL patients presented with an IPI score of 0–1, 59% with a score of 2–3, and 28% with a score of 4–5. The 5 year overall survival for patients with scores of 0–1 andr 4–5 are 56% and 25%, respectively, when treated with a recommended CHOP or a CHOP-like chemotherapy regimen.[66] The addition of etoposide or the proteasome inhibitor, bortezomib, to CHOP regimens has modestly increased overall and complete response rates.[67] Autologous hematopoietic stem cell transplantation likewise appears to improve the results of CHOP regimens. Small studies have found that patients with refractory or relapsed AITL have positive responses to pralatrexate, romidepsin, belinostat, brentuximab vedotin, lenalidomide, alisertib, and mogamulizumab. These drugs are being further studied for their usefulness for refractory and relapsed as well as initially untreated AITL.[66]
##### Follicular T cell lymphoma[edit]
Follicular T cell lymphoma (FTCL), previously considered a variant of peripheral T cell lymphomas, was reclassified by the World Health Organization (2016) as a type of lymphoma in the category of angioimmunoblastic T cell lymphoma (AITL) and other nodal TFH cell lymphomas. This rare disorder is similar to AITL in that it is a lymph node-based malignancy or TFH cells; it differs from AITL in that it may be diagnosed at an early, limited, and comparatively less aggressive stage and that its tissue lesions lack characteristic features of AITL, e.g. the do not show vascular proliferation.[1] FTCL develops mostly in elderly individuals but has been reported in those as young as 27 years. Individuals commonly (~73% of cases) present with advanced stage III or IV disease characterized by lymphadenopathy involving neck, armpit, and/or groin areas (~86%); enlarged liver (~25%) and/or spleen (25%); and malignant cell infiltrations in the bone marrow (~25%) or, rarely, tonsils, salivary glands, and/or hard palate. B symptoms of fever, night sweats, and weight loss occur in <33% of cases. Laboratory abnormalities include a positive Coombs test with or without accompanying autoimmune hemolytic anemia (~50%) and elevated blood levels of lactic acid dehydrogenase (45%) and gamma globulins (19%).[68] Two histologic patterns of pathology in involved lymphoid tissues are described, 1) a follicular lymphoma-like pattern in which malignant TFH cells form nodules and 2) a progressive transformation of germinal centers-like pattern in which malignant TFH cells from irregularly-shaped nodules surrounded by immunoglobulin D positive mantle cells (a type of B cell). Large B cell immunoblasts and occasional Reed-Sternberg cell-like B cells may also occupy these lesions. In 50–60% of FTCL, one or more of these B cell types, but not the malignant TFH cells, are infected with EBV, apparently in a latency II stage.[1] Diagnosis of FTCLL depends on clinical and laboratory findings, the pathology of the lesions, and identification in lymph nodes, skin, or other lesions of TFH cells as defined by their expression of appropriate marker proteins (e.g. PD-1, ICOS, CXCL13, CXCR5, and TOX).
No controlled studies on the treatment of the disease have been reported. Stage I and II localized FTCL has been treated with surgery, X-ray therapy, PUVA therapy, topical steroids, chlormethine, and/or carmustine. More extensive stage III and IV disease has been treated with single chemotherapy drugs (e.g. methotrexate); multiple chemotherapy drug regimens (e.g. CHOP, R-CVP (i.e. rituximab, cytoxin, vincristine, prednisone); with Rituximab, bortezomib, thalidomide, interferon-alpha, interferon-gamma, bexarotene, gemcitabine; and with hematopoietic stem cell transplantation. Responses to these treatments were variable and often disappointing.[69] Most recently, however, bendamustine combined with rituximab or rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone have achieved partial response rates of >90% even in patients with advanced stage disease. While complete remission rates are substantially lower than 90% and treated patients have inevitably relapsed, these regiments are recommended front-line treatments for symptomatic advanced stage follicular lymphoma.[70]
### Systemic Epstein–Barr virus-positive T cell lymphoma of childhood[edit]
Systemic EBV-positive T cell lymphoma of childhood (TCLC) is an extremely rare and aggressive T cell lymphoma that occurs almost exclusively in children, adolescents, and young adults. It occurs more frequently in Asians and Latin Americans. The disease develops as a complication or progression of either Epstein–Barr virus-positive infectious mononucleosis (EPV+ IM) or chronic active Epstein–Barr virus infection (CAEBV).,[1] that is, as a worsening of the signs/symptoms some 3 weeks after the onset of an EBV+ IM-like disease or an any time during the course of CAEBV. It presents in these diseases as the onset of progressive enlargements of the liver and spleen, worsening liver dysfunction, new skin rashes, pancytopenia (i.e. falls in the blood levels of leukocytes, red blood cells, and platelets), hemophagocytosis (i.e. ingestion of blood cells by histiocytes) in bone marrow and spleen), a coagulopathy (poor blood clotting), sepsis, and/or one or multiple organ failures. Unlike the findings in IM, patients with TCLC show low or undetectable levels of circulating IgM antibody but detectable levels of IgG antibody directed against EBV capsular antigens. Involved tissues contain rapidly proliferating small or, less commonly, somewhat larger lymphoid cells. These cells are EBV+ cytotoxic T cells and express CD8, CD3, CD2, TAI1, and granzyme but not CD56. Rarely and mostly in the setting of CAEBV disease, these cells are CD4\+ T cells or a mixture of CD4+ and CD8\+ T cells. The disease is usually fatal within weeks of diagnosis. A few cases have responded to the HLH-2004 chemotherapy protocol (etoposide, dexamethasone, cyclosporine A or, in selected cases, corticosteroids and intrathecal methotrexate, which may or many not be followed by hematopoietic stem cell transplantation.[14]
### Epstein–Barr virus-associated aggressive NK cell leukemia[edit]
Main article: Aggressive NK cell leukemia
Epstein–Barr virus-associated aggressive NK cell leukemia (EBV+ ANKL) is a rare NK cell malignancy that occurs most often in Asians and young to middle-aged adults. It sometimes evolves directly from other NK cell proliferative disorders such as, particularly in younger individuals, chronic active EBV infection (CAEBV).[1] A study conducted in China found that all or almost all patients presented with B symptoms (weight loss, fever, night sweats) and an enlarged liver and/or spleen but not lymph nodes. Laboratory studies revealed pancytopenia (i.e. reduced numbers of circulating white blood cells, platelets, and red blood cells) in almost all cases; small increases in the levels of circulating large granular lymphocytes shown or suspected of being malignant NK cells in 50% of cases; increased numbers of NK cells in the bone marrow in all cases; greatly increased blood levels of lactic acid dehydrogenase and β2 microglobulin in all cases; liver damage as defined by increased blood levels of enzymes, total bilirubin, and indirect total bilirubin plus increased blood clotting time in ≥30% of cases; and CT scans showing non-specific interstitial pneumonia in 90% of cases. All cases had EPV+ lymphocytes in bone marrow and tissue infiltrates; occasional cases had also has circulating EBV+ lymphocytes.[71] In other studies, EBV+ NK cells have been reported in 85–100% of cases.[1] Histological analysis of involved tissues generally reveals infiltrates of large granular EBV+ NK cells mixed with benign inflammatory cells that are often focused around small blood vessels; these findings are usually accompanied by tissue necrosis. The EBV+ NK cells express CD56 antigen and are malignant[72] with EBV in its latency II phase. The NK cells expression relatively high levels of the LMP1 viral protein; this protein may activate the NF-κB cell signaling pathway and thereby stimulate EBV-infected cells to proliferate.[1] These findings occur in ~84% of individuals with what is termed "classic ANKL." Some 16% of individuals present with "sub-acute ANKL". The latter individuals exhibit signs and symptoms resembling infectious mononucleosis that endures for 3–15 months and then takes the fulminant course characteristic of classic ANKL.[73]
Classic and sub-acute ANKL rapidly progress to life-threatening hemophagocytosis, disseminated intravascular coagulation, liver failure, renal failure, respiratory failure, and/or multiple organ failures. Median survival times in studies that did not distinguish between classic and sub-acute disease were ~60 days. A study of Chinese patients reported medium survival times of 49 days for classic and 215 days for sub-acute ANKL. Treatments for ANKL have typically used intensive chemotherapy regimens, either CHOP plus L-asparaginase or, alternatively, SMILE (i.e. dexamethasone, methotrexate, leucovorin, ifosfamide, L-Asparaginase, and etoposide. However, results with these regimens have been poor with little improvement in survival times.[71] More recently, addition of autologous autologous hematopoietic stem cell transplantation to these chemotherapy regiments has modestly improved medium survival times in both classic and sub-acute disease. Further studies to find more effective treatment regimens for ANKL are needed. One regimen under such consideration uses AspaMetDex (L-asparagenase, methotrexate, dexamethasone) for induction therapy and SMILE for consolidation therapy followed by autologous hemotopoietic stem cell transplantation.[73]
### Intravascular NK/T-cell lymphomas[edit]
Main article: Intravascular lymphomas
Two extremely rare types of the intravascular lymphomas, intravascular NK-cell lymphoma and intravascular T- cell lymphoma, are associated with, and appear driven by, EBV infection of NK- and cytotoxic T-cells, respectively. At presentation, afflicted individuals (age range 23–81 years) exhibit skin lesions; less commonly, signs and symptoms of central nervous system involvement; and, in a minority of cases, signs and symptoms of bone marrow, liver, kidneys, ovaries, and/or cervix involvement.[74] At that time or shortly thereafter, they show clear signs of having a disseminated disease such as fever, weight loss, night sweats, arthralgias, jaundice, decreased numbers of circulating red blood cells, white blood cells, and/or platelets, and the involvement of multiple organs.[75] The two intravascular lymphomas are, in general, aggressive and rapidly progressive diseases with patients usually responding poorly to treatment and having short (often less than 12 months) survival times.[76][77][78][79]
## EBV-associated immunodeficiency-related lymphoproliferative disorders[edit]
EBV infection is associated with various lymphoproliferative disorders that have a high frequency of occurring in individuals with any one of several different types of immunodeficiency. This category of EBV+ LPD is heterogeneous, involving EBV-infected B cells, T cells, and/or histiocytic/dendritic cells. These LPD also occur in immunocompetent individuals and are detailed in the above section entitled "EBV+ B cell lymphoproliferative diseases."
### EBV-related and HIV-related LPD[edit]
Individuals carrying the human immunodeficiency virus (HIV, the cause of AIDS) have an increased incidence of developing a LPD ranging from polyclonal lymphocyte proliferation (i.e. the abnormal proliferation of two or more clones of benign lymphocytes) to overtly malignant LPD. The EBV-related and HIV-related malignant LPD are: diffuse large B cell lymphomas with plasmablastic features (DLBL); a distinctive subtype of DLBL termed primary central nervous system lymphoma (PCNSL); Burkitt lymphoma (BL); Hodgkin lymphoma (HL); plasmablastic lymphoma (PBL); and primary effusion lymphoma (PEL) (also termed pleural effusion lymphoma). (PEL cases are infected not only with HIV and in most cases EBV but also Kaposi's sarcoma-associated herpesvirus (HHV8) in all cases.) These LPD are B cell diseases which the World Health Organization (2016) divides into those occurring in: 1) immune-competent, HIV-negative individuals; 2) HIV+ individuals; and 3) individuals with other immunodeficiency disorders.[1] The LPD occurring in immune-competent, HIV-negative individuals are detailed in the above section entitled EBV+ B cell lymphoproliferative diseases. The LPD occurring predominantly in HIV-positive individuals are detailed in the following Table which gives the percentage of the LPD that are EBV+, the latency phase of the virus in each LPD, and some factors expressed by the hosts malignant cells which promote the development, growth, and/or survival of the malignant cells in each LPD.
LPD type Percent EBV+ Latency phase[1] Latent EBV genes expressed[1] Factors promoting the development, growth and/or survival of malignant cells
DLBL 30–40% III all Mutations or changes in the expression of TNFAIP3, MYC, and/or BCL6 genes.[12]
PCNSL 90–100% III all Mutations in MYD88 and CD79B genes and copy number gains at the programmed death ligand 1 and programmed death ligand 2 gene loci on chromosome 9.[80]
BL 30–40% I EBERs Translocations and/or mutations in the MYC and/or TP53 genes.[1]
HL 100% II LMP1, LMP2, LMP2A, EBNA1, EBERs The products proteins of some of these viral genes stimulate the NFkB cell signaling pathway.[1]
PBL 70–80% possible I/II EBERs, rarely LMP1 Translocations, amplifications, and other causes (e.g. mutations in the PRDM1 gene) lead to the overexpression of the MYC gene.[49]
PEL 90% possible I/II EBNA1, LMP2A, EBERs Concurrent infection with HHV8 and this virus's expression of its transforming proteins (e.g. LANA1) appears responsible for the disorder.[49]
Further findings and the treatment of EBV-related and HIV-related LPD are given in the "EBV+ B cell lymphoproliferative diseases" section. Except for the possible exclusion of PEL,[50] these treatments should include continuance or, in individuals who have not yet been treated for AIDS, the institution of anti-HIV combination drug regimens.[1] In the category of EBV+ LPD occurring in individuals who are immunodeficient due to other causes than HIV infection, the other causes for immune-incompetency include:
1) Immune deficiency diseases such as common variable immunodeficiency, X-linked agammaglobulinemia, hypogammaglobulinemia,[37] the Wiskott–Aldrich syndrome, ataxia telangiectasia, the radiosensitive forms of severe combined immunodeficiency disease (SCID), the autoimmune lymphoproliferative syndrome, and the WHIM syndrome.[10]
2) Immunosuppressive drug therapy, particularly methotrexate and regimens including methotrexate.[37]
3) Genetic defects in the expression of genes for XIAP encoding the X-linked inhibitor of apoptosis protein, IAK encoding interleukin-2 inducible T cell kinase, CD27 encoding a receptor in the tumor necrosis factor receptor superfamily, STK4 encoding serine/threonine-protein kinase 4, 1CTPS1 encoding CTP sythetase, CORO1A encoding coronin 1A, APDS encoding activated phosphatidylinositide 3-kinase, CD16 encoding FcγRIII, GATA2 encoding GATA-binding factor 2 (a transcription factor), and MCM4 encoding the DNA replication licensing factor, MCM4.[10]
4) Inflammatory/autoimmune diseases such as chronic hepatitis, ulcerative colitis, retroperitoneal fibrosis, and primary biliary cholangitis.[37]
5) Chronic autoimmune and inflammatory diseases such as rheumatoid arthritis, Graves' disease, Giant-cell arteritis, sarcoidosis, and severe psoriasis), particularly in individuals receiving immunosuppressive drugs for these diseases.[52]
Treatment of these diseases generally follows that for the LPD occurring in immune-competent individuals but include discontinuing or reducing the dosages of immunosuppressive drugs and addressing the underlying disease causing immunodeficiency.[49]
### Post-transplant lymphoproliferative disorders[edit]
Main article: Post-transplant lymphoproliferative disorder
Post-transplant lymphoproliferative disorders (PTLD) are a group of LPD that occur following solid organ or hematopoietic stem cell transplantation. It is due to the immunosuppressive drug regimens that accompany these transplantations. EBV-positivity occurs in 60–80% of these cases and, unlike EBV-negative cases, EBV+ cases develop more often within the first year after transplantation. The 2026 WHO classification divides these disorders into:[49]
1) Non-destructive PTLD: this disorder is characterized by hyperplasia of plasma cells, florid hyperplasia of lymph node follicles, and infectious mononucleosis. All three of these are non-malignant disorders that involve lesions admixed with non-destructive proliferations of plasma which are usually EBV-negative, EBV-negative B cells, and rare EBV-positive T cells.
2) Monomorphic PTLD: this disorder is a B- or T cell lymphoma. It includes only aggressive lymphomas while excluding all indolent forms of LPD except for the inclusion of EBV-positive mucocutaneous ulcer The EBV+ positivity of cells involved in these PTLD are similar to those occurring in immune-competent individuals. In EBV-positive mucocutaneous ulcer, lesions commonly include EBV-positive plasma cells.
3) Classic Hodgkin lymphoma: This HD malignancy is characterized by have EBV+ cells its lesions. These lesions are otherwise similar to those occurring in immune competent individuals.
The virus in the three PTLD are in latency phase III and express most if not all of their latency genes including, in particular, LMP1 and LMP2A. The latter two EBV latency proteins are thought to promote the development and progression these PTLD by activating the NFkB pathway in and thereby stimulating the proliferation and survival of the infected host cells.[49]
## EBV-associated histiocytic-dendritic disorders[edit]
### Inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma[edit]
Main article: Follicular dendritic cell sarcoma
Inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma is a variant of follicular dendritic cell sarcoma (FDCS). FDCS is a rare malignancy of follicular dendritic cells (FD cells). These myofibroblast-like cells are derived from the stroma (i.e. connective tissue) of lymph nodes and other lymphatic tissue and therefore are not lymphocytes. FD cells express several markers expressed by lymphocytes; occupy the germinal centers of lymphoid tissues; and attract, stimulate the differentiation and proliferation of, and present foreign antigens to B-cells.[12] The FD cells in FDCS may derive from follicular lymphoma cells by the process of transdifferentiation.[12] FDCS affects primarily young to middle-aged adults of both sexes. Afflicted individuals commonly present with painless, slowly progressive swelling of cervical lymph nodes. About 33% of cases exhibit (with or without cervical lymph node swelling) tumors of skin, mediastinum, tonsils, gastrointestinal tract, and/or soft tissues. Some 10–20% of all cases are associated with precedent or contemporary Castleman disease, a benign lymphoproliferative disorder.[81] There are two histopathological forms of FDCS, conventional and inflammatory. Conventional FDCS exhibits spindle-shaped FD cells in a background of small lymphocytes; inflammatory FDCS exhibits relatively rare spindle-shaped cells in a background of plasma cells, middle- to large-sized lymphocytes, and Reed–Sternberg-like cells. EBV is associated only with the inflammatory form of FDCS.[82] In these cases, the FD cells express FD-cell markers (e.g. CD21, CD23, CD35, clusterin, podoplanin, gamma-synuclein)[81] and in >90% of cases products of the virus's EBER[82] and LMLP1 genes.[1] These cells are infected with EBV in latency II or III phases while the background cells are EBV-negative and not malignant. In one study, 2 of five 5 individuals with EBV+ FDCS had an activating mutation in the BRAF. While a role for EBV in FDCS remains unproven, LMP1 is able to transform rat fibroblasts into malignant-like behavior in vitro. The expression of LMP1 by FD cells might contribute to the malignancy of these cells in FDCS.[1]
Overall, patients with FDCS have local recurrence rates of 40–50 and a long term mortality rates due to the disease of ~20%.[81] However, FDSC, particularly in cases with only lymph node involvement, usually has an indolent course with a low rate (~10%) of metastasis. In these cases, surgical removal appears to be the treatment of choice; the role of radiation and chemotherapy here is not well-defined. Cases with extranodal involvement, especially those with abdominal tumors, have a higher metastatic rate (~20%). Chemotherapy regimens remain the mainstay for treating disseminated FDCS. However, these regimens (e.g. CHOP, ICE, and ABVD) have produced variable results. Too few individuals have been treated with allogeneic hematopoietic stem cell transplantation to determine its role in treating FDSC.[12] Further studies on the usefulness of radiation, chemotherapy, bone marrow transplantation, and newer non-chemotherapy drugs such as the BRAF oncogene inhibitor, vemurafenib, (for individuals with the BRAF oncogene), are needed.[81]
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34. ^ a b c d Chavez JC, Sandoval-Sus J, Horna P, Dalia S, Bello C, Chevernick P, Sotomayor EM, Sokol L, Shah B (August 2016). "Lymphomatoid Granulomatosis: A Single Institution Experience and Review of the Literature". Clinical Lymphoma, Myeloma & Leukemia. 16 Suppl: S170–4. doi:10.1016/j.clml.2016.02.024. PMID 27521314.
35. ^ Roschewski M, Wilson WH (2012). "Lymphomatoid granulomatosis". Cancer Journal (Sudbury, Mass.). 18 (5): 469–74. doi:10.1097/PPO.0b013e31826c5e19. PMID 23006954. S2CID 8958101.
36. ^ a b c d e f g h Tang VK, Vijhani P, Cherian SV, Ambelil M, Estrada-Y-Martin RM (2018). "Primary pulmonary lymphoproliferative neoplasms". Lung India. 35 (3): 220–230. doi:10.4103/lungindia.lungindia_381_17. PMC 5946555. PMID 29697079.
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38. ^ Sigamani E, Chandramohan J, Nair S, Chacko G, Thomas M, Mathew LG, Pulimood S, Manipadam MT (2018). "Lymphomatoid granulomatosis: A case series from South India". Indian Journal of Pathology & Microbiology. 61 (2): 228–232. doi:10.4103/IJPM.IJPM_471_17. PMID 29676363.
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42. ^ Murthy SL, Hitchcock MA, Endicott-Yazdani TR, Watson JT, Krause JR (October 2017). "Epstein-Barr virus-positive diffuse large B-cell lymphoma". Proceedings (Baylor University. Medical Center). 30 (4): 443–444. doi:10.1080/08998280.2017.11930222. PMC 5595389. PMID 28966459.
43. ^ García-Barchino MJ, Sarasquete ME, Panizo C, Morscio J, Martinez A, Alcoceba M, Fresquet V, Gonzalez-Farre B, Paiva B, Young KH, Robles EF, Roa S, Celay J, Larrayoz M, Rossi D, Gaidano G, Montes-Moreno S, Piris MA, Balanzategui A, Jimenez C, Rodriguez I, Calasanz MJ, Larrayoz MJ, Segura V, Garcia-Muñoz R, Rabasa MP, Yi S, Li J, Zhang M, Xu-Monette ZY, Puig-Moron N, Orfao A, Böttcher S, Hernandez-Rivas JM, Miguel JS, Prosper F, Tousseyn T, Sagaert X, Gonzalez M, Martinez-Climent JA (May 2018). "Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia". The Journal of Pathology. 245 (1): 61–73. doi:10.1002/path.5060. PMID 29464716. S2CID 4870618.
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46. ^ Smedby KE, Ponzoni M (November 2017). "The aetiology of B cell lymphoid malignancies with a focus on chronic inflammation and infections". Journal of Internal Medicine. 282 (5): 360–370. doi:10.1111/joim.12684. PMID 28875507.
47. ^ Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa K (October 2002). "Pyothorax-associated lymphoma: a review of 106 cases". Journal of Clinical Oncology. 20 (20): 4255–60. doi:10.1200/JCO.2002.09.021. PMID 12377970.
48. ^ a b c d Boyer DF, McKelvie PA, de Leval L, Edlefsen KL, Ko YH, Aberman ZA, Kovach AE, Masih A, Nishino HT, Weiss LM, Meeker AK, Nardi V, Palisoc M, Shao L, Pittaluga S, Ferry JA, Harris NL, Sohani AR (March 2017). "Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation". The American Journal of Surgical Pathology. 41 (3): 299–312. doi:10.1097/PAS.0000000000000775. PMID 28195879. S2CID 3521190.
49. ^ a b c d e f g h i Linke-Serinsöz E, Fend F, Quintanilla-Martinez L (July 2017). "Human immunodeficiency virus (HIV) and Epstein–Barr virus (EBV) related lymphomas, pathology view point". Seminars in Diagnostic Pathology. 34 (4): 352–363. doi:10.1053/j.semdp.2017.04.003. PMID 28506687.
50. ^ a b Arora N, Gupta A, Sadeghi N (July 2017). "Primary effusion lymphoma: current concepts and management". Current Opinion in Pulmonary Medicine. 23 (4): 365–370. doi:10.1097/MCP.0000000000000384. PMID 28399009. S2CID 4514140.
51. ^ Bhavsar T, Lee JC, Perner Y, Raffeld M, Xi L, Pittaluga S, Jaffe ES (June 2017). "KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder: New Findings and Review of the Literature". The American Journal of Surgical Pathology. 41 (6): 795–800. doi:10.1097/PAS.0000000000000823. PMC 5423846. PMID 28248818.
52. ^ a b Tchernonog E, Faurie P, Coppo P, Monjanel H, Bonnet A, Algarte Génin M, Mercier M, Dupuis J, Bijou F, Herbaux C, Delmer A, Fabiani B, Besson C, Le Gouill S, Gyan E, Laurent C, Ghesquieres H, Cartron G (April 2017). "Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group". Annals of Oncology. 28 (4): 843–848. doi:10.1093/annonc/mdw684. PMID 28031174.
53. ^ Hunter NB, Vogt S, Ambinder RF (December 2017). "Treatment of HIV-Associated Lymphomas: The Latest Approaches for Optimizing Outcomes". Oncology (Williston Park, N.Y.). 31 (12): 872–7, 884. PMID 29297171.
54. ^ Sekiguchi Y, Shimada A, Ichikawa K, Wakabayashi M, Sugimoto K, Ikeda K, Sekikawa I, Tomita S, Izumi H, Nakamura N, Sawada T, Ohta Y, Komatsu N, Noguchi M (2015). "Epstein–Barr virus-positive multiple myeloma developing after immunosuppressant therapy for rheumatoid arthritis: a case report and review of literature". International Journal of Clinical and Experimental Pathology. 8 (2): 2090–102. PMC 4396324. PMID 25973110.
55. ^ a b c Yan J, Wang J, Zhang W, Chen M, Chen J, Liu W (April 2017). "Solitary plasmacytoma associated with Epstein–Barr virus: a clinicopathologic, cytogenetic study and literature review". Annals of Diagnostic Pathology. 27: 1–6. doi:10.1016/j.anndiagpath.2016.09.002. PMID 28325354.
56. ^ Huang WR, Liu DH (September 2018). "Peripheral T cell Lymphomas: Updates in Allogeneic Hematopoietic Stem Cell Transplantation". Chinese Medical Journal. 131 (17): 2105–2111. doi:10.4103/0366-6999.239315. PMC 6111674. PMID 30127221.
57. ^ Gratzinger D, de Jong D, Jaffe ES, Chadburn A, Chan JK, Goodlad JR, Said J, Natkunam Y (February 2017). "T- and NK-Cell Lymphomas and Systemic Lymphoproliferative Disorders and the Immunodeficiency Setting: 2015 SH/EAHP Workshop Report-Part 4". American Journal of Clinical Pathology. 147 (2): 188–203. doi:10.1093/ajcp/aqw213. PMC 6248696. PMID 28395105.
58. ^ a b Yamaguchi M, Miyazaki K (December 2017). "Current treatment approaches for NK/T-cell lymphoma". Journal of Clinical and Experimental Hematopathology. 57 (3): 98–108. doi:10.3960/jslrt.17018. PMC 6144191. PMID 28679966.
59. ^ Yamaguchi M, Oguchi M, Suzuki R (September 2018). "Extranodal NK/T-cell lymphoma: Updates in biology and management strategies". Best Practice & Research. Clinical Haematology. 31 (3): 315–321. doi:10.1016/j.beha.2018.07.002. PMID 30213402.
60. ^ a b c Broccoli A, Zinzani PL (March 2017). "Peripheral T-cell lymphoma, not otherwise specified". Blood. 129 (9): 1103–1112. doi:10.1182/blood-2016-08-692566. PMID 28115372.
61. ^ Nemani S, Korula A, Agrawal B, Kavitha ML, Manipadam MT, Sigamani E, George B, Srivastava A, Viswabandya A, Mathews V (May 2018). "Peripheral T cell lymphoma: Clinico-pathological characteristics & outcome from a tertiary care centre in south India". The Indian Journal of Medical Research. 147 (5): 464–470. doi:10.4103/ijmr.IJMR_1108_16. PMC 6094517. PMID 30082570.
62. ^ Khan N, Ozkaya N, Moskowitz A, Dogan A, Horwitz S (September 2018). "Peripheral T-cell lymphoma—are we making progress?". Best Practice & Research. Clinical Haematology. 31 (3): 306–314. doi:10.1016/j.beha.2018.07.010. PMID 30213401.
63. ^ Ludvigsen M, Bjerregård Pedersen M, Lystlund Lauridsen K, Svenstrup Poulsen T, Hamilton-Dutoit SJ, Besenbacher S, Bendix K, Møller MB, Nørgaard P, d'Amore F, Honoré B (October 2018). "Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified". Blood Advances. 2 (19): 2533–2542. doi:10.1182/bloodadvances.2018019893. PMC 6177647. PMID 30291111.
64. ^ Mosalpuria K, Bociek RG, Vose JM (January 2014). "Angioimmunoblastic T-cell lymphoma management". Seminars in Hematology. 51 (1): 52–8. doi:10.1053/j.seminhematol.2013.11.008. PMID 24468316.
65. ^ Fujisawa M, Chiba S, Sakata-Yanagimoto M (2017). "Recent Progress in the Understanding of Angioimmunoblastic T-cell Lymphoma". Journal of Clinical and Experimental Hematopathology. 57 (3): 109–119. doi:10.3960/jslrt.17019. PMC 6144190. PMID 29279549.
66. ^ a b Broccoli A, Zinzani PL (April 2017). "Angioimmunoblastic T-Cell Lymphoma". Hematology/Oncology Clinics of North America. 31 (2): 223–238. doi:10.1016/j.hoc.2016.12.001. PMID 28340875.
67. ^ Lunning MA, Vose JM (March 2017). "Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma". Blood. 129 (9): 1095–1102. doi:10.1182/blood-2016-09-692541. PMID 28115369.
68. ^ Hu S, Young KH, Konoplev SN, Medeiros LJ (November 2012). "Follicular T-cell lymphoma: a member of an emerging family of follicular helper T-cell derived T-cell lymphomas". Human Pathology. 43 (11): 1789–98. doi:10.1016/j.humpath.2012.05.002. PMID 22959759.
69. ^ Wang JY, Nguyen GH, Ruan J, Magro CM (May 2017). "Primary Cutaneous Follicular Helper T-Cell Lymphoma: A Case Series and Review of the Literature". The American Journal of Dermatopathology. 39 (5): 374–383. doi:10.1097/DAD.0000000000000695. PMID 28375859.
70. ^ Yazdy MS, Ujjani C (June 2017). "Current challenges in the management of follicular lymphoma". International Journal of Hematologic Oncology. 6 (1): 13–24. doi:10.2217/ijh-2017-0003. PMC 6171972. PMID 30302218.
71. ^ a b Zhang H, Meng Q, Yin W, Xu L, Lie L (July 2013). "Adult aggressive natural killer cell leukemia". The American Journal of the Medical Sciences. 346 (1): 56–63. doi:10.1097/MAJ.0b013e3182764b59. PMID 23241562. S2CID 32910828.
72. ^ Lima M (October 2015). "Extranodal NK/T cell lymphoma and aggressive NK cell leukaemia: evidence for their origin on CD56+bright CD16-/+dim NK cells". Pathology. 47 (6): 503–14. doi:10.1097/PAT.0000000000000275. PMID 26166665. S2CID 5264015.
73. ^ a b Tang YT, Wang D, Luo H, Xiao M, Zhou HS, Liu D, Ling SP, Wang N, Hu XL, Luo Y, Mao X, Ao QL, Huang J, Zhang W, Sheng LS, Zhu LJ, Shang Z, Gao LL, Zhang PL, Zhou M, Zhou KG, Qiu LG, Liu QF, Zhang HY, Li JY, Jin J, Fu L, Zhao WL, Chen JP, Du X, Huang G, Wang QF, Zhou JF, Huang L (December 2017). "Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes". Blood Cancer Journal. 7 (12): 660. doi:10.1038/s41408-017-0021-z. PMC 5802497. PMID 29263371.
74. ^ Bi Y, Huo Z, Liang Z, Meng Y, Jia C, Shi X, Song L, Luo Y, Ling Q, Liu T (July 2015). "Intravascular NK-cell lymphoma: a case report and review of the literature". Diagnostic Pathology. 10: 84. doi:10.1186/s13000-015-0336-7. PMC 4488042. PMID 26126576.
75. ^ Yan J, Zhang F, Luo D, Yao S, Chen Y, Xu F, Luo X, He J, Liu Y (2017). "Intravascular NK/T-cell lymphoma: a series of four cases". International Journal of Clinical and Experimental Pathology. 10 (9): 9541–9550. PMC 6965900. PMID 31966830.
76. ^ Zanelli M, Mengoli MC, Del Sordo R, Cagini A, De Marco L, Simonetti E, Martino G, Zizzo M, Ascani S (November 2018). "Intravascular NK/T-cell lymphoma, Epstein-Barr virus positive with multiorgan involvement: a clinical dilemma". BMC Cancer. 18 (1): 1115. doi:10.1186/s12885-018-5001-6. PMC 6238309. PMID 30442097.
77. ^ Gleason BC, Brinster NK, Granter SR, Pinkus GS, Lindeman NI, Miller DM (February 2008). "Intravascular cytotoxic T-cell lymphoma: A case report and review of the literature". Journal of the American Academy of Dermatology. 58 (2): 290–4. doi:10.1016/j.jaad.2006.12.022. PMID 18222325.
78. ^ Wang L, Chen S, Ma H, Shi D, Huang C, Lu C, Gao T, Wang G (September 2015). "Intravascular NK/T-cell lymphoma: a report of five cases with cutaneous manifestation from China". Journal of Cutaneous Pathology. 42 (9): 610–7. doi:10.1111/cup.12515. PMID 25931234. S2CID 23046075.
79. ^ Melchers RC, Willemze R, Jansen PM, Daniëls LA, Vermeer MH, Quint KD (June 2019). "A rare case of cutaneous Epstein-Barr virus-negative intravascular cytotoxic T-cell lymphoma". JAAD Case Reports. 5 (6): 548–551. doi:10.1016/j.jdcr.2019.04.013. PMC 6581970. PMID 31245517.
80. ^ Grommes C, DeAngelis LM (July 2017). "Primary CNS Lymphoma". Journal of Clinical Oncology. 35 (21): 2410–2418. doi:10.1200/JCO.2017.72.7602. PMC 5516483. PMID 28640701.
81. ^ a b c d Wu A, Pullarkat S (February 2016). "Follicular Dendritic Cell Sarcoma". Archives of Pathology & Laboratory Medicine. 140 (2): 186–90. doi:10.5858/arpa.2014-0374-RS. PMID 26910224.
82. ^ a b Kazemimood R, Saei Hamedani F, Sharif A, Gaitonde S, Wiley E, Giulianotti PC, Groth JV (2017). "A Rare Case of Epstein-Barr Virus Negative Inflammatory Pseudotumor-like Follicular Dendritic Cell Sarcoma Presenting as a Solitary Colonic Mass in a 53-Year-Old Woman; Case Report and Review of Literature". Applied Immunohistochemistry & Molecular Morphology. 25 (5): e30–e33. doi:10.1097/PAI.0000000000000405. PMID 27299190. S2CID 3872007.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Epstein–Barr virus-associated lymphoproliferative diseases | None | 2,369 | wikipedia | https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus-associated_lymphoproliferative_diseases | 2021-01-18T18:33:57 | {"wikidata": ["Q60791668"]} |
Uveal melanoma (155720) is the most common primary intraocular malignancy. Monosomy 3, which is an unusual finding in most tumors, is present in approximately 50% of uveal melanomas and is significantly correlated with metastatic disease. To obtain positional information on putative tumor suppressor genes on chromosome 3, Tschentscher et al. (2001) investigated tumors from 333 patients by comparative genomic hybridization, microsatellite analysis, or conventional karyotype analysis. A partial deletion of the long arm was found in 8 tumors, and the smallest region of deletion overlap (SRO) spanned 3q24-q26. They found 6 tumors with a partial deletion of the short arm and defined a second SRO of about 2.5 Mb in 3p25. Tschentscher et al. (2001) interpreted their findings as suggesting a role for 2 tumor suppressor genes in metastasizing uveal melanoma: one on 3q, here designated UVM1, and a second on 3p25, here designated UVM2 (606661). The involvement of 2 tumor suppressor genes may explain the loss of an entire chromosome 3 in metastatic uveal melanomas.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| MELANOMA, UVEAL, SUSCEPTIBILITY TO, 1 | c0346388 | 2,370 | omim | https://www.omim.org/entry/606660 | 2019-09-22T16:10:14 | {"doid": ["6039"], "omim": ["606660"], "orphanet": ["39044"], "synonyms": ["Alternative titles", "UVM1"]} |
Pelvis justo major (also called "Giant Pelvis") is a rare condition of the adult female pelvis where the pelvis flairs above the Iliopectineal line.[1] It is 1.5 or more times larger than an average pelvis in every direction and is at least 42 cm (16.5 inches) biiliac width. Even though this condition is classified as a congenital abnormality, it is not a medical disease or abnormality of the pelvis (as the pelvis is a true gynecoid shape, only larger).
Women with this condition, at the time of delivery, may have a precipitous birth.[2] There is virtually no resistance of the huge pelvic opening to the size of a newborn so only the soft parts resist the birth. With a huge Justo Major Pelvis, there is no pelvic bone "molding" of the fetal head.[3] With the average pelvic size (2/3 or less Justo Major size) the usual pelvic molding process slows the birth, resulting in a slow and gradual stretching of the vaginal opening for primiparous women. When a huge Justo Major Pelvis allows such an extremely rapid vaginal birth, there can be tears of the perineal soft tissues. At the time of delivery the strong uterine contractions and maternal bearing down almost instantly overwhelm the integrity of a tightened and previously unstretched vaginal orifice. This is often the case if such women have not previously practiced vaginal stretching to the degree that allows such an instant birthing, especially so for a primiparous woman. This "instant delivery" problem causes many OBGYN doctors to stress the importance of women with a huge pelvis practicing pre-delivery vaginal stretching to avoid perineal injury.
Such a large size for the female pelvis is present in less than one in a thousand adult women. When women reach their maximum pelvis size, often by 21 years of age, if they have a huge pelvis the resulting big hips will not go away—no matter how much they diet, as bone will not shrink. It is not unusual for such women, whose pear shape is due to a huge pelvis, to give up watching calories for smaller hips... leading to obesity. However, such pear shaped obese women do not necessarily have a huge pelvis and a measurement scan or anthropometry by calipers is required to diagnose the Justo Major condition. The incidence of Justo Major Pelvis is not found to be a strictly standard deviation type variation as it follows a tail skewed deviation to the right. Incidence varies with geographic regions of the world (e.g. Poland has a high incidence). Justo Major Pelvis is classified as congenital and thought to be partially inherited, especially from the maternal side.
## References[edit]
1. ^ Stedman's Medical dictionary 1914 (3rd ed.). Lippincott Williams & Wilkins. 1914. pp. 692–.
2. ^ James Clifton Edgar (1912). The Practice of obstetrics. P. Blakiston's Son & Company. pp. 605–.
3. ^ Fleetwood Churchill (1848). On the Theory and Practice of Midwifery. Lea and Blanchard. pp. 273–.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Pelvis justo major | c0265721 | 2,371 | wikipedia | https://en.wikipedia.org/wiki/Pelvis_justo_major | 2021-01-18T19:03:11 | {"umls": ["C0265721"], "icd-10": ["Q74.2"], "wikidata": ["Q7161813"]} |
A rare non-syndromic syndactyly characterized by mesoaxial reduction of fingers, complete syndactyly of the 3rd and 4th fingers with synostoses of the corresponding metacarpals and associated single phalanges, malformed thumbs, and hypoplasia and clinodactyly of the 5th finger. Preaxial webbing of toes with terminal phalangeal hypoplasia of all toes has been reported in association.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Mesoaxial synostotic syndactyly with phalangeal reduction | c1836206 | 2,372 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157801 | 2021-01-23T17:39:47 | {"gard": ["10590"], "mesh": ["C563721"], "omim": ["609432"], "umls": ["C1836206"], "icd-10": ["Q70.0", "Q70.2"], "synonyms": ["MSSD", "Syndactyly type 9", "Syndactyly, Malik-Percin type"]} |
Yellow nail syndrome
Other namesprimary lymphedema
Yellow nail syndrome: This patient has a 20-year history of severe lymphedema of her legs; thick, ridged, yellowish, hypercurved thumbnails (top right); similarly affected, yellow-green to brown toenails (bottom right); and bilateral, chylous pleural effusions. A sample of her chylous pleural fluid is shown to the left of the radiograph.
SpecialtyDermatology
Yellow nail syndrome, also known as "primary lymphedema associated with yellow nails and pleural effusion",[1]:849 is a very rare medical syndrome that includes pleural effusions, lymphedema (due to under development of the lymphatic vessels) and yellow dystrophic nails.[2] Approximately 40% will also have bronchiectasis. It is also associated with chronic sinusitis and persistent coughing. It usually affects adults.[3][4]:665[5]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 Epidemiology
* 7 History
* 8 References
* 9 External links
## Signs and symptoms[edit]
The nails are markedly thickened with yellow to yellow-green discoloration of the nails.[1]:792[6] They grow slowly, at a rate of 0.25 mm/week or less. The nails may have ridges and increased side-to-side curvature, reduction of the white crescent and detachment of the nail from the nailbed.[5] These nail abnormalities may also change over time.[5]
Most people with yellow nail syndrome (four fifths) have lymphedema; it is symmetrical and typically affects both legs. It is the first symptom of the condition in about a third. Involvement of the arms and face is more unusual, as is lymphedema of the abdomen with ascites (fluid collection in the abdominal cavity) and fluid collection around the heart.[5]
Various lung problems can occur in people with yellow nail syndrome. Many experience cough and shortness of breath. Forty percent of cases develop pleural effusions, which are collections of fluid in the pleural cavity (the space that contains the lungs and normally only has a minimal amount of fluid in it).[5] About half of all people with yellow nail syndrome have either recurrent chest infections or a chronic lung condition known as bronchiectasis which causes chronic production of sputum with episodes of worsening. Forty percent of people with yellow nail syndrome have chronic sinusitis.[5]
Yellow nail syndrome has been associated with some drugs, e.g. penicillamine, bucillamine and gold sodium thiomalate.[7]
It has also been associated with exposure to titanium from dental implants.[8]
## Genetics[edit]
Although it has been described in families, it has been suggested that it might not have a genetic link.[9]
## Diagnosis[edit]
The diagnosis is based on the combination of the symptoms. Generally, people are diagnosed with yellow nail syndrome if they have two or three of the three classical symptoms (yellow nails, lymphedema and pleural effusion). The nail changes are considered essential for the diagnosis, but they can be subtle.[5]
Pulmonary function testing can show obstruction of the airways. People with pleural effusions may show evidence of restriction in lung volumes due to the fluid. Analysis of the fluid in pleural effusions generally shows high levels of protein but low levels of cholesterol and lactate dehydrogenase, but about 30% of effusions are chylous (chylothorax) in that they have the characteristics of lymph.[5]
A lymphogram may be performed in people with lymphedema. This can show both under developed (hypoplastic) lymphatic ducts and dilated ducts. Dye may be found in the skin months after the initial test. Scintigraphy of lymph flow (lymphoscintigraphy) shows delays in drainage of lymph (sometimes asymmetrically), although this test can also be normal.[5]
## Treatment[edit]
Normal treatment for swelling and any respiratory problems is appropriate. Nutritional supplementation with Vitamin E in some studies has been shown to be effective in controlling nail changes.[3]
## Prognosis[edit]
People with yellow nail syndrome have been found to have a moderately reduced lifespan compared to people without the condition.[5]
## Epidemiology[edit]
The condition is thought to be rare, with approximately 150 cases described in the medical literature.[5]
## History[edit]
The condition was first described in 1964 by London physicians Peter Samman and William White.[10] Earlier cases may have been recorded in 1927 and 1962.[5]
## References[edit]
1. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
2. ^ "Yellow nail syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
3. ^ a b "Yellow nail syndrome. DermNet NZ". Retrieved 2008-03-19.
4. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
5. ^ a b c d e f g h i j k l Maldonado, Fabien; Ryu, Jay H (July 2009). "Yellow nail syndrome". Current Opinion in Pulmonary Medicine. 15 (4): 371–375. doi:10.1097/MCP.0b013e32832ad45a. PMID 19373089.
6. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1020. ISBN 978-1-4160-2999-1.
7. ^ Nanda S; Dorville F (2009). "Yellow nail syndrome". Canadian Medical Association Journal. 181 (9): 614. doi:10.1503/cmaj.080255. PMC 2764757. PMID 19770240.
8. ^ Berglund, F; Carlmark, B (2010). "Titanium, Sinusitis, and the Yellow Nail Syndrome". Biological Trace Element Research. 143 (1): 1–7. doi:10.1007/s12011-010-8828-5. PMC 3176400. PMID 20809268.
9. ^ Hoque SR, Mansour S, Mortimer PS (June 2007). "Yellow nail syndrome: not a genetic disorder? Eleven new cases and a review of the literature". Br. J. Dermatol. 156 (6): 1230–4. doi:10.1111/j.1365-2133.2007.07894.x. PMID 17459037.
10. ^ Samman, PD; White, WF (April 1964). "The "yellow nail" syndrome". The British Journal of Dermatology. 76 (4): 153–7. doi:10.1111/j.1365-2133.1964.tb14499.x. PMID 14140738.
## External links[edit]
Classification
D
* ICD-10: L60.5
* OMIM: 153300
* MeSH: D056684
* SNOMED CT: 400211001
External resources
* MedlinePlus: 003247
* eMedicine: article/109403
* Orphanet: 662
* v
* t
* e
Disorders of skin appendages
Nail
* thickness: Onychogryphosis
* Onychauxis
* color: Beau's lines
* Yellow nail syndrome
* Leukonychia
* Azure lunula
* shape: Koilonychia
* Nail clubbing
* behavior: Onychotillomania
* Onychophagia
* other: Ingrown nail
* Anonychia
* ungrouped: Paronychia
* Acute
* Chronic
* Chevron nail
* Congenital onychodysplasia of the index fingers
* Green nails
* Half and half nails
* Hangnail
* Hapalonychia
* Hook nail
* Ingrown nail
* Lichen planus of the nails
* Longitudinal erythronychia
* Malalignment of the nail plate
* Median nail dystrophy
* Mees' lines
* Melanonychia
* Muehrcke's lines
* Nail–patella syndrome
* Onychoatrophy
* Onycholysis
* Onychomadesis
* Onychomatricoma
* Onychomycosis
* Onychophosis
* Onychoptosis defluvium
* Onychorrhexis
* Onychoschizia
* Platonychia
* Pincer nails
* Plummer's nail
* Psoriatic nails
* Pterygium inversum unguis
* Pterygium unguis
* Purpura of the nail bed
* Racquet nail
* Red lunulae
* Shell nail syndrome
* Splinter hemorrhage
* Spotted lunulae
* Staining of the nail plate
* Stippled nails
* Subungual hematoma
* Terry's nails
* Twenty-nail dystrophy
Hair
Hair loss/
Baldness
* noncicatricial alopecia: Alopecia
* areata
* totalis
* universalis
* Ophiasis
* Androgenic alopecia (male-pattern baldness)
* Hypotrichosis
* Telogen effluvium
* Traction alopecia
* Lichen planopilaris
* Trichorrhexis nodosa
* Alopecia neoplastica
* Anagen effluvium
* Alopecia mucinosa
* cicatricial alopecia: Pseudopelade of Brocq
* Central centrifugal cicatricial alopecia
* Pressure alopecia
* Traumatic alopecia
* Tumor alopecia
* Hot comb alopecia
* Perifolliculitis capitis abscedens et suffodiens
* Graham-Little syndrome
* Folliculitis decalvans
* ungrouped: Triangular alopecia
* Frontal fibrosing alopecia
* Marie Unna hereditary hypotrichosis
Hypertrichosis
* Hirsutism
* Acquired
* localised
* generalised
* patterned
* Congenital
* generalised
* localised
* X-linked
* Prepubertal
Acneiform
eruption
Acne
* Acne vulgaris
* Acne conglobata
* Acne miliaris necrotica
* Tropical acne
* Infantile acne/Neonatal acne
* Excoriated acne
* Acne fulminans
* Acne medicamentosa (e.g., steroid acne)
* Halogen acne
* Iododerma
* Bromoderma
* Chloracne
* Oil acne
* Tar acne
* Acne cosmetica
* Occupational acne
* Acne aestivalis
* Acne keloidalis nuchae
* Acne mechanica
* Acne with facial edema
* Pomade acne
* Acne necrotica
* Blackhead
* Lupus miliaris disseminatus faciei
Rosacea
* Perioral dermatitis
* Granulomatous perioral dermatitis
* Phymatous rosacea
* Rhinophyma
* Blepharophyma
* Gnathophyma
* Metophyma
* Otophyma
* Papulopustular rosacea
* Lupoid rosacea
* Erythrotelangiectatic rosacea
* Glandular rosacea
* Gram-negative rosacea
* Steroid rosacea
* Ocular rosacea
* Persistent edema of rosacea
* Rosacea conglobata
* variants
* Periorificial dermatitis
* Pyoderma faciale
Ungrouped
* Granulomatous facial dermatitis
* Idiopathic facial aseptic granuloma
* Periorbital dermatitis
* SAPHO syndrome
Follicular cysts
* "Sebaceous cyst"
* Epidermoid cyst
* Trichilemmal cyst
* Steatocystoma
* simplex
* multiplex
* Milia
Inflammation
* Folliculitis
* Folliculitis nares perforans
* Tufted folliculitis
* Pseudofolliculitis barbae
* Hidradenitis
* Hidradenitis suppurativa
* Recurrent palmoplantar hidradenitis
* Neutrophilic eccrine hidradenitis
Ungrouped
* Acrokeratosis paraneoplastica of Bazex
* Acroosteolysis
* Bubble hair deformity
* Disseminate and recurrent infundibulofolliculitis
* Erosive pustular dermatitis of the scalp
* Erythromelanosis follicularis faciei et colli
* Hair casts
* Hair follicle nevus
* Intermittent hair–follicle dystrophy
* Keratosis pilaris atropicans
* Kinking hair
* Koenen's tumor
* Lichen planopilaris
* Lichen spinulosus
* Loose anagen syndrome
* Menkes kinky hair syndrome
* Monilethrix
* Parakeratosis pustulosa
* Pili (Pili annulati
* Pili bifurcati
* Pili multigemini
* Pili pseudoannulati
* Pili torti)
* Pityriasis amiantacea
* Plica neuropathica
* Poliosis
* Rubinstein–Taybi syndrome
* Setleis syndrome
* Traumatic anserine folliculosis
* Trichomegaly
* Trichomycosis axillaris
* Trichorrhexis (Trichorrhexis invaginata
* Trichorrhexis nodosa)
* Trichostasis spinulosa
* Uncombable hair syndrome
* Wooly hair nevus
Sweat
glands
Eccrine
* Miliaria
* Colloid milium
* Miliaria crystalline
* Miliaria profunda
* Miliaria pustulosa
* Miliaria rubra
* Occlusion miliaria
* Postmiliarial hypohidrosis
* Granulosis rubra nasi
* Ross’ syndrome
* Anhidrosis
* Hyperhidrosis
* Generalized
* Gustatory
* Palmoplantar
Apocrine
* Body odor
* Chromhidrosis
* Fox–Fordyce disease
Sebaceous
* Sebaceous hyperplasia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Yellow nail syndrome | c0221348 | 2,373 | wikipedia | https://en.wikipedia.org/wiki/Yellow_nail_syndrome | 2021-01-18T19:05:13 | {"gard": ["184"], "mesh": ["D056684"], "umls": ["C0221348"], "orphanet": ["662"], "wikidata": ["Q1786851"]} |
Lymphatic disease
SpecialtyLymphologist
Lymphatic disease is a class of disorders which directly affect the components of the lymphatic system.
Examples include Castleman's disease[1] and lymphedema.[2]
## Contents
* 1 Types
* 2 References
* 3 External links
## Types[edit]
Diseases and disorder
Hodgkin's Disease/Hodgkin's Lymphoma Hodgkin lymphoma This is a type of cancer of the lymphatic system. It can start almost anywhere in the body. It is believed to be caused by HIV, Epstein-Barr Syndrome, age, and family history. Symptoms include weight gain, fever, swollen lymph nodes, night sweats, itchy skin, fatigue, chest pain, coughing, or trouble swallowing.
Non-Hodgkin's Lymphoma
Lymphoma is usually malignant cancer. It is caused by the body producing too many abnormal white blood cells. It is not the same as Hodgkin's Disease. Symptoms usually include painless, enlarged lymph node or nodes in the neck, weakness, fever, weight loss, and anemia.
Lymphadenitis
Lymphadenitis is an infection of the lymph nodes usually caused by a virus, bacteria or fungi. Symptoms include redness or swelling around the lymph node.
Lymphangitis
Lymphangitis is an inflammation of the lymph vessels. Symptoms usually include swelling, redness, warmth, pain or red streaking around the affected area.
Lymphedema
Lymphedema is the chronic pooling of lymph fluid in the tissue. It usually starts in the feet or lower legs. It's also a side-effect of some surgical procedures.
Lymphocytosis
Lymphocytosis is a high lymphocyte count. It can be caused by an infection, blood cancer, lymphoma, or autoimmune disorders that are accompanied by chronic swelling.
## References[edit]
1. ^ "MedlinePlus: Lymphatic Diseases".
2. ^ "Lymphedema: Lymphatic Disorders: Merck Manual Home Edition".
## External links[edit]
Classification
D
* MeSH: D008206
* v
* t
* e
Lymphatic disease: organ and vessel diseases
Thymus
* Abscess
* Hyperplasia
* Hypoplasia
* DiGeorge syndrome
* Ectopic thymus
* Thymoma
* Thymic carcinoma
Spleen
* Asplenia
* Asplenia with cardiovascular anomalies
* Accessory spleen
* Polysplenia
* Wandering spleen
* Splenomegaly
* Banti's syndrome
* Splenic infarction
* Splenic tumor
Lymph node
* Lymphadenopathy
* Generalized lymphadenopathy
* Castleman's disease
* Intranodal palisaded myofibroblastoma
* Kikuchi disease
* Tonsils
* see Template:Respiratory pathology
Lymphatic vessels
* Lymphangitis
* Lymphangiectasia
* Lymphedema
* Primary lymphedema
* Congenital lymphedema
* Lymphedema praecox
* Lymphedema tarda
* Lymphedema–distichiasis syndrome
* Milroy's disease
* Secondary lymphedema
* Bullous lymphedema
* Factitial lymphedema
* Postinflammatory lymphedema
* Postmastectomy lymphangiosarcoma
* Waldmann disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Lymphatic disease | c0024228 | 2,374 | wikipedia | https://en.wikipedia.org/wiki/Lymphatic_disease | 2021-01-18T18:41:02 | {"mesh": ["D008206"], "umls": ["C0024228"], "wikidata": ["Q6708237"]} |
Not to be confused with Chondroma.
Chordoma
MRI of extensive clival chordoma in 17-year-old male patient, axial view. Tumor in the nasopharynx extending from nasal cavity to brainstem posteriorly is clearly visible.
SpecialtyOncology
Chordoma is a rare slow-growing neoplasm thought to arise from cellular remnants of the notochord. The evidence for this is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life.
In layman's terms, chordoma is a type of spinal cancer.[1]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Mechanism
* 4 Diagnosis
* 4.1 Classification
* 5 Treatment
* 6 Prognosis
* 7 Epidemiology
* 8 Society
* 9 Notable cases
* 10 References
* 11 External links
## Presentation[edit]
Sacral Bone Chordoma
Chordomas can arise from bone in the skull base and anywhere along the spine. The two most common locations are cranially at the clivus and in the sacrum at the bottom of the spine.[2]
## Genetics[edit]
MRI of extensive clival chordoma in 17-year-old male patient, sagittal view. Tumor in the nasopharynx extending from nasal cavity to brainstem posteriorly is clearly visible.
A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma.[3]
A possible association with tuberous sclerosis complex (TSC1 or TSC2) has been suggested.[4]
## Mechanism[edit]
* mTOR signaling is hyperactive in sporadic sacral chordomas: in one study 10 out of 10 sacral chordomas exhibited phosphorylation of Ribosomal protein s6 and EIF4EBP1 by immunohistochemistry[5]
* Partial or complete PTEN (gene) deficiency is observed in nearly all sacral chordomas[5]
* In a study of 49 chordomas Akt, TSC2, and EIF4EBP1 were phosphorylated in 92%, 96% and 98% of cases, respectively.[6]
* In a tissue microarray containing 21 chordomas Platelet-derived growth factor receptor-beta (PDGFR-b), epidermal growth factor receptor (EGFR), KIT (CD117) and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively.[7]
* The CDKN2A (p16) and CDKN2B (p15) loci on chromosome 9p21 are frequently deleted in chordomas[8] Another study found CDKN2A immunoreactivity in just 4% of cases.[6]
* 62% of chordomas express the High Molecular Weight Melanoma Associated Antigen, also known as Chondroitin sulfate proteoglycan 4 (CSPG4) which has been the target of immune therapy.[9]
* In 2009, scientists discovered that an inherited gene duplication is responsible for the familial form of this disorder.[10] Familial chordoma are rare, with an estimated rate of 0.4% in all Chordomas.[11]
## Diagnosis[edit]
In 2015 the first consensus guidelines for the diagnosis and treatment of chordoma were published in The Lancet Oncology.[12]
### Classification[edit]
Micrograph showing a chordoma. HPS stain.
There are three histological variants of chordoma: classical (or "conventional"),[13] chondroid and dedifferentiated.
* The histological appearance of classical chordoma is of a lobulated tumor composed of groups of cells separated by fibrous septa. The cells have small round nuclei and abundant vacuolated cytoplasm, sometimes described as physaliferous (having bubbles or vacuoles).
* Chondroid chordomas histologically show features of both chordoma and chondrosarcoma.
## Treatment[edit]
In most cases, complete surgical resection followed by radiation therapy offers the best chance of long-term control.[14] Incomplete resection of the primary tumor makes controlling the disease more difficult and increases the odds of recurrence. The decision whether complete or incomplete surgery should be performed primarily depends on the anatomical location of the tumor and its proximity to vital parts of the central nervous system.[citation needed]
Chordomas are relatively radioresistant, requiring high doses of radiation to be controlled. The proximity of chordomas to vital neurological structures such as the brain stem and nerves limits the dose of radiation that can safely be delivered. Therefore, highly focused radiation such as proton therapy and carbon ion therapy are more effective than conventional x-ray radiation.[15]
There are no drugs currently approved to treat chordoma, however a clinical trial conducted in Italy using the PDGFR inhibitor Imatinib demonstrated a modest response in some chordoma patients.[16] The same group in Italy found that the combination of imatinib and sirolimus caused a response in several patients whose tumors progressed on imatinib alone.Erlotinib like EGFR inhibitors have been also reported to be effective in Chordoma.[17] Though EGFR mutation is not present in chordoma yet EGFR expression might predict response to erlotinib (as shown in report by Dr Sameer Rastogi).[17]
A report of response to olaparib has been published.[18]
## Prognosis[edit]
In one study, the 10-year tumor free survival rate for sacral chordoma was 46%.[19] Chondroid chordomas appear to have a more indolent clinical course.
## Epidemiology[edit]
In the United States, the annual incidence of chordoma is approximately 1 in one million (300 new patients each year).[20]
There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families.[21]
While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma. Because genetic or hereditary risk factors for chordoma may exist, scientists at the National Cancer Institute are conducting a Familial Chordoma Study to search for genes involved in the development of this tumor.[22]
## Society[edit]
Expert Recommendations for the Diagnosis and Treatment of Chordoma is a handbook produced by the Chordoma Foundation, which summarizes recommendations developed by a group of over 40 leading doctors who specialize in caring for chordoma patients. It is available electronically in English, Chinese, Italian, Dutch, and Spanish and hardcopies are available in English and Spanish.[23]
## Notable cases[edit]
NFL player Craig Heyward was treated for a chordoma in 1998, which ended his career. While initially thought to be successfully removed, the tumor returned in 2005, and caused Heyward's death in May 2006.
Pro skateboarder Ray Underhill, a member of the Powell-Peralta Bones Brigade, battled chordoma for two years before succumbing to his disease in August 2008.
Cary Tennis, the popular advice columnist for Salon, announced in his column of November 19, 2009, that he had been diagnosed with a chordoma.
Former Spanish footballer José Enrique was diagnosed with chordoma in May 2018 and underwent surgery to remove the tumour in June of that year. He announced in April 2019 that he had been given the all clear.
## References[edit]
1. ^ National Cancer Institute (February 27, 2019). "Chordoma".
2. ^ "Primary Malignant Bone Tumors: Tumors of Bones and Joints: Merck Manual Professional". Retrieved 2009-01-04.
3. ^ Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ (2012). "Chordoma: current concepts, management, and future directions". Lancet Oncol. 13 (2): e69–76. doi:10.1016/S1470-2045(11)70337-0. PMID 22300861.
4. ^ Lee-Jones L, Aligianis I, Davies PA, et al. (September 2004). "Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2". Genes Chromosomes Cancer. 41 (1): 80–5. doi:10.1002/gcc.20052. PMID 15236319.
5. ^ a b Han S, Polizzano C, Nielsen GP, Hornicek FJ, Rosenberg AE, Ramesh V (March 2009). "Aberrant Hyperactivation of Akt and Mammalian Target of Rapamycin Complex 1 Signaling in Sporadic Chordomas". Clinical Cancer Research. 15 (6): 1940–6. doi:10.1158/1078-0432.CCR-08-2364. PMC 2701205. PMID 19276265.
6. ^ a b Presneau N, Shalaby A, Idowu B, Gikas P, Cannon SR, Gout I, Diss T, Tirabosco R, Flanagan AM (May 2009). "Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway". British Journal of Cancer. 100 (9): 1406–14. doi:10.1038/sj.bjc.6605019. PMC 2694420. PMID 19401700.
7. ^ Fasig JH, Dupont WD, LaFleur BJ, Olson SJ, Cates JM (February 2008). "Immunohistochemical analysis of receptor tyrosine kinase signal transduction activity in chordoma". Neuropathology and Applied Neurobiology. 34 (1): 95–104. doi:10.1111/j.1365-2990.2007.00873.x. PMID 17973908.
8. ^ Hallor KH, Staaf J, Jönsson G, Heidenblad M, Vult von Steyern F, Bauer HC, Ijszenga M, Hogendoorn PC, Mandahl N, Szuhai K, Mertens F (January 2008). "Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation". British Journal of Cancer. 98 (2): 434–42. doi:10.1038/sj.bjc.6604130. PMC 2361468. PMID 18071362.
9. ^ Schwab JH, Boland PJ, Agaram NP, Socci ND, Guo T, O'Toole GC, Wang X, Ostroumov E, Hunter CJ, Block JA, Doty S, Ferrone S, Healey JH, Antonescu CR (March 2009). "Chordoma and chondrosarcoma gene profile: implications for immunotherapy". Cancer Immunology, Immunotherapy. 58 (3): 339–49. doi:10.1007/s00262-008-0557-7. PMC 3426285. PMID 18641983.
10. ^ "Gene Duplication Identified in an Uncommon Form of Bone Cancer". 2009. Archived from the original on 2009-10-09. Retrieved 2009-10-09.
11. ^ Wang, Ke; Zhen, Wu; Tian, Kaibing; Hao, Shuyu; Zhang, Liwei; Zhang, Junting (November 2015). "Familial Chordoma: a case report and review of the literature". Oncology Letters. Oncology Letters 10(5). 10 (5): 2937–2940. doi:10.3892/ol.2015.3687. PMC 4665336. PMID 26722267.
12. ^ "First clinical guidelines for chordoma treatment published in The Lancet Oncology". 2015-02-19.
13. ^ Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH (November 2007). "Chordoma: the nonsarcoma primary bone tumor". The Oncologist. 12 (11): 1344–50. doi:10.1634/theoncologist.12-11-1344. hdl:2027.42/139965. PMID 18055855.
14. ^ Park L, Delaney TF, Liebsch NJ, Hornicek FJ, Goldberg S, Mankin H, Rosenberg AE, Rosenthal DI, Suit HD (2006). "Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor". Int J Radiat Oncol Biol Phys. 65: 1514–21. doi:10.1016/j.ijrobp.2006.02.059. PMID 16757128.
15. ^ Delaney TF, Liebsch NJ, Pedlow FX, Adams J, Dean S, Yeap BY, McManus P, Rosenberg AE, Nielsen GP, Harmon DC, Spiro IJ, Raskin KA, Suit HD, Yoon SS, Hornicek FJ (2009). "Sacral chordomas: Phase II Study of High-Dose Photon/Proton Radiotherapy in the Management of Spine Sarcomas". Int J Radiat Oncol Biol Phys. 74: 732–9. doi:10.1016/j.ijrobp.2008.08.058. PMC 2734911. PMID 19095372.
16. ^ Casali PG, Messina A, Stacchiotti S, et al. (2004). "Imatinib mesylate in chordoma" (PDF). Cancer. 101 (9): 2086–97. doi:10.1002/cncr.20618. hdl:2434/642716. PMID 15372471.
17. ^ a b Verma, S., Vadlamani, S.P., Shamim, S.A. Rastogi S et al. Partial response to erlotinib in a patient with imatinib-refractory sacral chordoma. Clin Sarcoma Res 10, 28 (2020). https://doi.org/10.1186/s13569-020-00149-1
18. ^ Gröschel S, Hübschmann D, Raimondi F, Horak P, Warsow G, Fröhlich M, Klink B, Gieldon L, Hutter B, Kleinheinz K, Bonekamp D, Marschal O, Chudasama P10,11, Mika J, Groth M, Uhrig S, Krämer S, Heining C, Heilig CE, Richter D, Reisinger E, Pfütze K, Eils R, Wolf S, von Kalle C, Brandts C, Scholl C, Weichert W, Richter S, Bauer S, Penzel R, Schröck E, Stenzinger A, Schlenk RF, Brors B, Russell RB, Glimm H, Schlesner M, Fröhling S (2019) Defective homologous recombination DNA repair as therapeutic target in advanced chordoma. Nat Commun 10(1):1635
19. ^ Fuchs B, Dickey ID, Yaszemski MJ, Inwards CY, Sim FH (2005). "Operative management of sacral chordoma". The Journal of Bone and Joint Surgery. American Volume. 87 (10): 2211–6. doi:10.2106/JBJS.D.02693. PMID 16203885.
20. ^ "College student fights his own cancer - Yahoo! News". Archived from the original on 2008-02-26. Retrieved 2008-02-20.
21. ^ Kelley MJ, Shi J, Ballew B, Hyland PL, Li WQ, Rotunno M, Alcorta DA, Liebsch NJ, Mitchell J, Bass S, Roberson D, Boland J, Cullen M, He J, Burdette L, Yeager M, Chanock SJ, Parry DM, Goldstein AM, Yang XR (2014). "Familial Chordoma Study of the T Gene". Hum Genet. 133 (10): 1289–97. doi:10.1007/s00439-014-1463-z. PMC 6938388. PMID 24990759.
22. ^ "Familial Chordoma Study". Archived from the original on 2009-02-14. Retrieved 2009-02-03.
23. ^ Expert Recommendations for the Diagnosis and Treatment of Chordoma
## External links[edit]
* Images of Chordoma - mostly radiological (CT and MRI scans), one autopsy image
* Research information on chordoma (WikiGenes)
Classification
D
* ICD-O: M9370/3
* OMIM: 215400
* MeSH: D002817
* DiseasesDB: 31483
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* eMedicine: med/2992 radio/169 orthoped/49
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*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Chordoma | c0008487 | 2,375 | wikipedia | https://en.wikipedia.org/wiki/Chordoma | 2021-01-18T18:37:09 | {"gard": ["1303"], "mesh": ["D002817"], "umls": ["C0008487"], "orphanet": ["178"], "wikidata": ["Q1076389"]} |
A number sign (#) is used with this entry because of evidence that Crouzon syndrome is caused by heterozygous mutation in the gene encoding fibroblast growth factor receptor-2 (FGFR2; 176943) on chromosome 10q26.
See also Crouzon syndrome with acanthosis nigricans (CAN; 612247), a distinct disorder caused by a specific mutation in the FGFR3 gene (A391E; 134934.0011).
Description
Crouzon syndrome is an autosomal dominant disorder characterized by craniosynostosis causing secondary alterations of the facial bones and facial structure. Common features include hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism (Reardon et al., 1994; Glaser et al., 2000).
Clinical Features
Crouzon (1912) first described this syndrome in a family.
Shiller (1959) observed autosomal dominant transmission of Crouzon craniofacial dysostosis in 23 family members spanning 4 generations. There was marked variability in both cranial and facial manifestations. Dodge et al. (1959) described 3 patients with typical Crouzon disease; 2 of these had a positive family history and one was sporadic.
Devine et al. (1984) described a completely cartilaginous trachea without ring formation in a child with Crouzon syndrome who continued to have respiratory distress despite surgical repair of choanal stenosis. Death from respiratory problems occurred at the age of 23 months.
Cohen et al. (1993) reported a mother, son, and daughter in whom serial photographs documented an insidious and late onset of exorbitism and midfacial retrusion. Papilledema resulting from increased intracranial pressure secondary to a reduction in cranial vault size was found in the 4.5-year-old daughter, whereas optic nerve sheath swelling was found on CT scan in the son.
Reddy et al. (1990) described 4 patients who presented between the ages of 2 and 9 years with 'delayed holocalvarial synostosis.'
Cinalli et al. (1995) reviewed the neurosurgical complications of Crouzon syndrome in a series of 68 patients. Nineteen of these patients required treatment for progressive hydrocephalus and 72.7% of these patients had chronic tonsillar herniation, which was symptomatic in 6 individuals. Four individuals had syringomyelia and another had a respiratory standstill, whereas the remaining patient had painful torticollis.
### Phenotypic Variability
Bagheri-Fam et al. (2015) reported a 15-year-old girl with Crouzon-like craniosynostosis and a mutation in the FGFR2 gene who also exhibited 46,XY complete gonadal dysgenesis. Craniofacial features included brachycephalic craniosynostosis for which she required surgery, proptosis with downslanting palpebral fissures, and low-set dorsally rotated ears. The patient also had short stature and limited movement of the elbows and knees, but no anomalies of the hands or feet. She presented with delayed puberty, primary amenorrhea, female external genitalia, and Mullerian structures, and underwent gonadectomy due to the presence of bilateral ovarian tumors. Histologic analysis revealed bilateral dysgerminoma, which apparently developed from preexisting gonadoblastoma. The gonads lacked seminiferous tubules, and only a few Sertoli- and Leydig-like cells were detected.
Inheritance
Fogh-Andersen (1943), Flippen (1950), and Shiller (1959) traced Crouzon craniosynostosis through 4 generations of 3 different families, consistent with autosomal dominant inheritance. Pinkerton and Pinkerton (1952) observed the disorder in a mother and 2 of her 3 daughters.
Vulliamy and Normandale (1966) identified 14 cases of Crouzon disease in 4 generations of a family with several instances of male-to-male transmission.
Jones et al. (1975) found evidence of paternal age effect in new mutations for this disorder.
Rollnick (1988) described 2 brothers with Crouzon syndrome born to normal, unrelated parents, and proposed germinal mosaicism as the explanation. Kreiborg and Cohen (1990) suggested germinal mosaicism as the basis for 2 affected sibs with the same mother but different fathers. The mother and both fathers were completely normal.
Goriely et al. (2010) reported a girl with a mild form of Crouzon syndrome, confirmed by genetic analysis, whose clinically unaffected mother was found to be somatic mosaic for a heterozygous FGFR2 mutation. Levels of maternal somatic mosaicism for the mutation were estimated to range from 3.3% in hair roots to 14.1% in blood. Since her daughter inherited the same mutation, it was presumed to be present also in the mother's germline. The findings underlined the importance of parental molecular testing for accurate genetic counseling of the risk of recurrence for Crouzon syndrome, which is most often due to a de novo mutation resulting from a paternal age effect.
Mapping
In a large kindred with Crouzon craniofacial dysostosis, Preston et al. (1994) found linkage to 3 loci (D10S190, D10S209, and D10S216) spanning a 13-cM region on chromosome 10q. A maximum pairwise lod score of 4.42 at theta = 0.0 was obtained with D10S190 and the addition of a second kindred produced a combined pairwise lod score of 5.32 at theta = 0.0. In a note added in proof, Preston et al. (1994) stated that a newly available highly informative marker, D10S587, located 7 cM distal to D10S209, increased the 2-family multipoint lod score for linkage between CFD1 and D10S209 to 7.3 at theta = 0.0. Two of the genetic marker loci were within 10q25-q26.
Molecular Genetics
Reardon et al. (1994) identified mutations in the FGFR2 gene (see, e.g., 176943.0001-176943.0006) in 9 of 20 patients with Crouzon syndrome. Because no evidence of genetic heterogeneity on the basis of linkage studies had been found, Reardon et al. (1994) concluded that mutations in parts of the FGFR2 gene other than in the B exon were responsible for the remaining cases.
Jabs et al. (1994) demonstrated mutations in the FGFR2 gene in patients with Crouzon syndrome as well as in patients with Jackson-Weiss syndrome (JWS; 123150).
Charnas et al. (1989) described affected male and female second cousins, and suggested either incomplete penetrance or another molecular predisposition ('premutation'). However, Meyers et al. (1995) reported that the 2 patients described by Charnas et al. (1989) had mutations in different genes: the patient with classic Crouzon syndrome had an FGFR2 mutation (176943.0009), whereas the second cousin had Crouzon syndrome with acanthosis nigricans (612247) due to the FGFR3 A391E mutation (134934.0001).
In 22 of 41 probands with Crouzon syndrome or Pfeiffer syndrome (101600), Glaser et al. (2000) identified 11 different FGFR2 mutations. All the mutations were paternal in origin. Advanced paternal age was noted for the fathers of patients with Crouzon syndrome or Pfeiffer syndrome, compared with the fathers of control individuals. This finding extended previous information on advanced paternal age for sporadic FGFR2 mutations causing Apert syndrome (101200) and FGFR3 mutations causing achondroplasia (100800).
In a 15-year-old girl with Crouzon-like craniosynostosis and 46,XY complete gonadal dysgenesis, Bagheri-Fam et al. (2015) sequenced the candidate gene FGFR2 and identified heterozygosity for the C342S mutation (176943.0003) that had previously been identified in 1 patient diagnosed with Crouzon syndrome, 1 patient diagnosed with Jackson-Weiss syndrome (123150), and 1 patient with an 'extreme' Antley-Bixler phenotype (207410). DNA from the proband's parents was unavailable for study. Whole-exome sequencing to search for potential modifier variants influencing the proband's phenotype revealed single-nucleotide variants or indels in 193 genes. Bagheri-Fam et al. (2015) noted that although none of the changes were located in 63 genes associated with disorders of sex development, the patient did carry novel changes or indels in 35 genes that, in mice, are expressed in pre-Sertoli cells at the time of sex determination.
Population Genetics
Cohen and Kreiborg (1992) estimated that Crouzon syndrome represents approximately 4.8% of cases of craniosynostosis at birth. The birth prevalence was estimated to be 16.5 per million births.
Animal Model
Eswarakumar et al. (2006) generated mice with a Crouzon-like craniosynostosis induced by a dominant mutation in the mesenchymal splice form of Fgfr2 (Fgfr2c) (C342Y; 176943.0001), and observed ocular proptosis, a rounded cranium, fusion of the coronal sutures, and a significantly shortened facial region. Expression of the C342Y mutation in cis with the L424A and R426A mutations of the juxtamembrane domain resulted in attenuation of signaling pathways by selective uncoupling between the docking protein Frs2a (607743) and activated Fgfr2c, thus preventing premature fusion of sutures and resulting in normal skull development. Eswarakumar et al. (2006) also demonstrated that attenuation of Fgfr signaling in a calvaria organ culture with an Fgfr inhibitor prevented premature fusion of sutures without adversely affecting the development of the skull.
History
On the basis of an affected brother and sister with unaffected nonconsanguineous parents, Juberg and Chambers (1973) suggested the existence of a recessive form of Crouzon disease.
### Pseudo-Crouzon Syndrome
Franceschetti (1953) described a seemingly distinct disorder under the designation cranial dysostosis with pronounced digital impressions, or 'pseudo-Crouzon disease.' However, Gorlin (1982) concluded that it is not distinct from Crouzon disease. According to Franceschetti's appraisal, in Crouzon disease and pseudo-Crouzon disease, the pronounced digital impressions, or convolutional markings, are identical, and the essential difference is in the face: in pseudo-Crouzon disease, there is no prognathism, the nose is not curved, and divergent squint is usually lacking. Prominent forehead and some degree of exophthalmos are features. Franceschetti (1968) proposed that Walsh (1957) described a case of pseudo-Crouzon disease as Crouzon disease. None of Franceschetti's cases was familial, but Dolivo and Gillieron (1955) described affected brother and sister whose mother, grandmother, and great-grandmother were said to have oxycephaly.
INHERITANCE \- Autosomal dominant HEAD & NECK Head \- Craniosynostosis \- Brachycephaly Face \- Frontal bossing \- Maxillary hypoplasia \- Mandibular prognathism Ears \- Conductive hearing loss \- Atretic external auditory canals Eyes \- Optic atrophy \- Shallow orbits \- Proptosis \- Hypertelorism \- Strabismus \- Exposure conjunctivitis/keratitis \- Poor vision Nose \- Parrot-like nose Mouth \- Lateral palatal swellings Teeth \- Dental crowding RESPIRATORY Nasopharynx \- Sleep apnea GENITOURINARY Internal Genitalia (Female) \- Dysgerminoma (in 1 patient) SKELETAL Skull \- Craniosynostosis (coronal, sagittal, lambdoid sutures) \- Calcification of stylohyoid ligament Spine \- Cervical spine abnormalities NEUROLOGIC Central Nervous System \- Mental retardation, occasional \- Seizures \- Frequent headaches MISCELLANEOUS \- Associated with increased paternal age MOLECULAR BASIS \- Caused by mutations in the fibroblast growth factor receptor 2 gene (FGFR2, 176943.0001 ) ▲ 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
| CROUZON SYNDROME | c2931196 | 2,376 | omim | https://www.omim.org/entry/123500 | 2019-09-22T16:42:43 | {"doid": ["2339"], "mesh": ["D003394"], "omim": ["123500"], "orphanet": ["207"], "synonyms": ["Crouzon craniofacial dysostosis", "Alternative titles", "CRANIOFACIAL DYSOSTOSIS, TYPE I", "CROUZON CRANIOFACIAL DYSOSTOSIS"], "genereviews": ["NBK1455"]} |
A number sign (#) is used with this entry because of evidence that the Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is caused by mutation in the gene encoding glypican-3 (GPC3; 300037) on chromosome Xq26.
Some evidence suggests that disruption of the GPC4 gene (300168), which is adjacent to the GPC3 gene, may also cause the disorder (see MOLECULAR GENETICS).
Description
Simpson-Golabi-Behmel syndrome is an X-linked condition characterized by pre- and postnatal overgrowth, coarse facies, congenital heart defects, and other congenital abnormalities (Xuan et al., 1999). It shows phenotypic similarities to Beckwith-Wiedemann syndrome (BWS; 130650), another overgrowth syndrome.
See also Simpson-Golabi-Behmel syndrome type 2 (SGBS2; 300209), which has been associated with a mutation in the CXORF5 gene (300170) on chromosome Xp22.
Clinical Features
Simpson et al. (1975) reported 2 male first cousins, sons of sisters, who had a distinctive facial appearance, including a large protruding jaw, widened nasal bridge, upturned nasal tip, and enlarged tongue. Other features included broad stocky appearance and broad, short hands and fingers. One of the patients had clefting of the lower lip. Intelligence was normal. The family referred to the appearance as 'bulldog'-like. Laboratory tests excluded hypothyroidism. Close linkage with the Xg blood group locus was excluded.
Kaariainen (1981) observed a tall (192 cm) 40-year-old man with operated pectus excavatum, ventricular septal defect, central cleft of the lower lip, peculiar cup-shaped ears with knobbiness and nodularity, short clubbed terminal phalanges, low-pitched voice, and cataracts developing at age 35. The parents, who came from different parts of Finland, were 170 and 160 cm tall. A brother, height 180 cm, died at age 18 years of ventricular septal defect and pulmonary hypertension. He looked like the surviving brother and quite different from other members of the family. Kaariainen (1982) concluded that the disorder was the same as that described by Simpson et al. (1975).
Golabi and Rosen (1984) reported a family in which 4 males in 4 sibships spanning 3 generations connected through females had prenatal and postnatal overgrowth; short, broad, upturned nose; large mouth, midline groove of tongue, inferior alveolar ridge and lower lip; submucous cleft palate; 13 ribs; Meckel diverticulum; intestinal malrotation; coccygeal skin tag and bony appendage; hypoplastic index fingernails; unilateral postaxial polydactyly; and bilateral syndactyly of fingers 2 and 3. Mental retardation was also a feature. The carrier mother of the propositus had a large mouth, coccygeal skin tag and bony appendage, and hypoplastic index fingernails. Behmel et al. (1988) suggested that the mental retardation in the family reported by Golabi and Rosen (1984) may have had a basis unrelated to the rest of the syndrome. Intelligence in the dysplasia gigantism syndrome is usually normal or only mildly retarded. Chen et al. (1993) reported the birth of a fifth affected male in the family reported by Golabi and Rosen (1984) and provided a follow-up of a patient who was 8 years old at the time of the initial report. He was 190 cm tall, had coarse facial features, micrognathia, short fingers, and dental abnormalities. Problems with speech and psychosocial development were also described. The newborn member of the family and a second unrelated male with this syndrome were found to have congenital diaphragmatic hernia. On the basis of these cases, Chen et al. (1993) noted that radiologic findings include flaring of the iliac wings, narrow sacroiliac notches, and the presence of 2 carpal ossification centers as a newborn ('advanced bone age').
In a pedigree pattern consistent with X-linked recessive inheritance, Behmel et al. (1984) observed 11 male newborns with a syndrome similar to that described by Simpson et al. (1975): elevated birth weight and length; disproportionately large head with coarse, distinctive facies; short neck; slight obesity; and broad, short hands and feet. The affected males who reached adulthood attained heights of about 2 m; their unusual facial and general appearance and clumsiness, remarkable during infancy and childhood, became somewhat less conspicuous. In all but 1, intelligence was normal, as it was in the 2 cases of Simpson et al. (1975). Behmel et al. (1988) provided follow-up on the family reported by Behmel et al. (1984) and added a second Austrian family. They concluded on the basis of these studies that the syndrome was identical to that reported by Simpson et al. (1975) and Golabi and Rosen (1984).
Opitz (1984) reported a family in which 3 boys born to half sisters were affected. The nose in affected males was particularly similar to that in the patients of Golabi and Rosen (1984). Opitz et al. (1988) provided follow-up of 1 of the patients reported by Opitz (1984). He died at age 25 months without attaining any psychomotor development and with a neurologic picture of irritability, hypotonia, seizures, deafness, and possible cortical blindness. Autopsy showed spongiform degeneration of brainstem and cerebrum; this patient may have had a different disorder.
Kajii and Tsukahara (1984) reported a possible case, which was originally described by Tsukahara et al. (1984) as 'a Weaver-like syndrome.' Garganta et al. (1988) and Garganta and Bodurtha (1992) concluded on the basis of 2 affected brothers with overgrowth, macrocephaly, polydactyly, supernumerary nipples, and a characteristic facial appearance that mental retardation is not a consistent feature. One of the boys had pulmonic stenosis and cleft palate. One of the boys also had creases of the posterior helix, suggesting the Beckwith-Wiedemann syndrome. Garganta et al. (1988) suggested that the Simpson dysmorphia syndrome and Golabi-Rosen syndrome are the same disorder. Neri et al. (1988) reported an affected kindred. They commented on the high frequency of infant death, a finding noted by others, and stated that postaxial hexadactyly of the hands is an occasional feature. They suggested the designation 'Simpson-Golabi-Behmel syndrome.' An affected patient reported by Gurrieri et al. (1992) also had postaxial polydactyly and extra nipples.
Hughes-Benzie et al. (1992) reported a family with 6 affected males in 5 sibships in 3 generations. All had pre- and postnatal overgrowth, with 2 adult males attaining heights over 195 cm. Other features included coarse facies with hypertelorism, broad nasal root, cleft palate, full lips with a midline groove in the lower lip, grooved tongue with tongue tie, prominent mandible, congenital heart defects, arrhythmias, supernumerary nipples, splenomegaly, large dysplastic kidneys, cryptorchidism, hypospadias, and postaxial hexadactyly. All affected individuals were of normal intelligence. One affected male died at age 19 months of a neuroblastoma. Eight carriers who showed varying manifestations of the syndrome were identified.
Ireland et al. (1993) presented a 5-generation family. Overgrowth was present in 4 affected males and 3 out of 4 carrier females. The facial features in affected males included facial asymmetry with hypertelorism and upward slanting palpebral fissures. In addition, they had a broad nose, thin lips, and a prominent mandible. The palate was high-arched, the tongue was grooved and tethered with an anterior notch, and there was a groove in the lower lip. None of the affected males was mentally retarded. One of the affected males had bilateral hydronephrosis and a nonfunctioning kidney; another had bilateral cataracts diagnosed at age 2 years and retinal detachment at age 5 years. Facial features in carrier females included short, narrow palpebral fissures, upturned nasal tip with a prominent columella, and a prominent chin. Both affected males and carrier females showed extra lumbar and thoracic vertebrae and accessory nipples.
From a review of reported cases, Garganta and Bodurtha (1992) concluded that early perinatal and infant mortality is high in patients with SGBS. Terespolsky et al. (1995) commented on the wide clinical range in reported cases of SGBS, ranging from a mild form associated with long-term survival to an early lethal form with multiple congenital anomalies and severe mental retardation. They found 8 reported families in which affected individuals died in infancy.
Konig et al. (1991) suggested that cardiac arrhythmias may be a major component of the SGB syndrome and can be responsible for death in early infancy and perhaps for cardiac arrest in the adult. Lin et al. (1999) concluded that cardiac abnormalities of any type are common in SGBS, occurring perhaps in almost one-half of cases, with cardiovascular malformations seen in one-third of cases.
Neri et al. (1998) reviewed the clinical and molecular aspects of SGBS. They emphasized that an increased risk of neoplasia in SGBS must be kept in mind, especially in young patients. They stated that Wilms tumor of the kidney had been found in several members of affected families in Canada (Hughes-Benzie et al., 1992; Xuan et al., 1994).
Kim et al. (1999) reported choledochal cysts in SGB syndrome. The patient was a new member of a family with this disorder previously reported by Chen et al. (1993) and Golabi and Rosen (1984). The diagnosis of SGBS had been suspected prenatally because of the family history and prenatal ultrasound findings of polyhydramnios, macrosomia, double-bubble sign suggestive of duodenal atresia, bilateral clubfoot, and visualization of a penis indicating male gender. At birth the length was 55 cm (97%). He had a coarse facial appearance, vertical furrows between the eyebrows, increased interpupillary distance, bifid uvula but no cleft lip or palate, and macrostomia. He had low-set, large floppy ears. The choledochal cyst was discovered at operation for other intraabdominal anomalies. Kim et al. (1999) provided an updated pedigree of the family with 7 affected individuals in 3 generations.
Griffith et al. (2009) reported 3 brothers with SGBS, aged 20 months, 4 years, and 6 years, all of whom had cryptorchidism. The eldest brother also had chordee of the penis, penoscrotal hypospadias, and penoscrotal transposition requiring multiple surgeries. The authors stated that this was the first SGBS patient with such anomalies to survive beyond the neonatal period, and suggested that a range of genital anomalies should be considered a nonrandom feature of SGBS.
Other Features
Cureton et al. (2007) described a 2-year-old boy with SGBS who presented with a hepatic lesion, which upon resection was found to be a vascular malformation. The authors suggested that, in addition to developing visceral solid malignancies, SGBS patients may also be at risk for developing vascular malformations.
Penisson-Besnier et al. (2008) reported a 44-year-old man with classic SGBS, confirmed by genetic analysis (300037.0011), who presented with acute internal carotid artery dissection. Radiography showed arterial redundancies of the affected artery. The authors postulated that the overgrowth involved in SGBS may have caused an increase in the length of the carotid, leading to coiling and thus to a greater risk of dissection.
Inheritance
Simpson-Golabi-Behmel syndrome typically shows X-linked recessive inheritance. However, some female mutation carriers may show mild features, presumably due to skewed X-chromosome inactivation. Yano et al. (2011) reported a Jordanian family in which 3 sibs, a boy and a dizygotic twin boy and girl pair, had SGBS due to a truncating mutation in the GPC3 gene inherited from their mother, who had very subtle features of the disorder. The 2 boys had the classic disorder, including overgrowth, coarse facies, macroglossia, pectus excavatum, and developmental delay, whereas the girl had milder but suggestive features, such as developmental delay, macrocephaly, patent ductus arteriosus, and diaphragmatic hernia. The mother had normal intelligence and very mild signs, such as slight coarse facies and macrostomia. X-inactivation studies of blood, which is of mesodermal origin and appropriately reflects GPC3 expression, showed that the affected daughter had a wildtype:mutant ratio of 20-29:71-80 favoring expression of the mutant allele, whereas the mother had a 57:43 ratio with slight favoring of the normal allele. X-inactivation ratios were different in other tissues. Overall, the results provided an explanation for the different phenotypic manifestations of SGBS in the 2 female mutation carriers in this family.
Diagnosis
### Differential Diagnosis
Hughes-Benzie et al. (1992) drew attention to the superficial similarities in the appearance of pedigrees segregating in an X-linked recessive pattern and those exhibiting an autosomal dominant pattern with imprinting of specific genes. As an illustration of the confusion, they referred to a family misdiagnosed as having Beckwith-Wiedemann syndrome, who was found to have SGBS based on clinical findings of postaxial polydactyly, midline groove in the lower lip, and more severely affected males (Niikawa et al., 1986; case 4). Shared clinical features of BWS and SGBS include macrosomia, macroglossia, cleft palate, visceromegaly, earlobe creases, hernias, neonatal hypoglycemia, and a risk of embryonal tumors.
Xuan et al. (1994) pointed to the report by Punnett et al. (1974) of a female with a putative diagnosis of Beckwith-Wiedemann syndrome and a balanced reciprocal (X;1)(q26;q12) translocation. Xuan et al. (1994) suggested that the description of the young woman was entirely compatible with SGBS and that the translocation may have disrupted the SGBS gene. Punnett (1994) reexamined this 23-year-old patient who, in addition to typical manifestations, had diaphragmatic hernia and pulmonic valve stenosis, and concluded that she actually had SGBS.
Verloes et al. (1995) commented on the difficulties in the differential diagnosis of overgrowth syndromes in the neonatal period and the phenotypic overlap of BWS, SGB syndrome, and Perlman syndrome (267000). They suggested that it may be necessary to add genital ambiguity, hydramnios, and nephroblastomatosis to the clinical spectrum of Simpson-Golabi-Behmel syndrome and to keep in mind a possible risk for embryonal tumors in patients with this syndrome.
Gertsch et al. (2010) reported a male infant initially diagnosed with Timothy syndrome (601005) after birth on the basis of QT interval prolongation in the neonatal period and syndactyly. At day 7 of life, the patient received an implantable cardioverter-defibrillator (ICD). However, genetic testing did not identify a mutation in the CACNA1C gene (114205), thus excluding a diagnosis of Timothy syndrome. Reevaluation of the patient showed that the syndactyly was postaxial and with bony fusion, not consistent with that observed in Timothy syndrome. Repeat genetic testing identified a truncating mutation in the GPC3 gene, confirming the diagnosis of SGBS. Other features in this infant included prenatal nuchal translucency on fetal imaging, high alpha-fetoprotein levels in the mother during pregnancy, macrosomia, hypoplastic index fingers, submucosal cleft palate, bifid uvula, and coarse facial features. The mother, who also carried the mutation, had tall stature, dolichocephaly, high-arched palate, pectus excavatum, joint laxity, and nonspecific T-wave abnormalities on EKG. The patient was found to have a normal QT interval at age 9 months, and the ICD was removed. Gertsch et al. (2010) emphasized the importance of distinguishing between Timothy syndrome and SGBS, since the former has a high incidence of neonatal mortality. They also noted that transient QT prolongation had not been reported in SGBS.
Mapping
By linkage analysis in a large family segregating SGBS, Hughes-Benzie et al. (1992) found linkage to chromosome Xcen-q21.3 (maximum lod score of 2.81 at marker DXYS68.)
Ireland et al. (1993) presented preliminary data supporting linkage of SGBS to Xqcen-q22 markers. In more extensive linkage analyses of the family reported by Ireland et al. (1993), Xuan et al. (1994) mapped the putative SGBS locus to Xq26; the closest linkage was to HPRT (308000) with a maximum lod score of 7.45 at theta = 0.00. Recombinations between SGBS and Xq markers placed the disease locus in the interval between DXS425 and DXS1123 on Xq25-q27. Orth et al. (1994) confirmed these data by the finding of close linkage of the disease locus and the HPRT gene (maximum lod = 4.45 at theta = 0.00) in an Austrian and an Italian family.
Molecular Genetics
### GPC3 Gene
Pilia et al. (1996) identified microdeletions in the GPC3 gene that cosegregated with SGBS in 3 affected families.
In affected members of a family described by Xuan et al. (1994), Xuan et al. (1999) identified a 13-bp deletion in the GPC3 gene (300037.0001). Xuan et al. (1999) confirmed their previous suggestion that a female in the family who had multiple thoracic hemivertebrae, Sprengel deformity of her right shoulder, and Wilms tumor did not carry the SGBS exon 2 deletion of the GPC3 gene. Xuan et al. (1999) suggested that the presence of skeletal abnormalities and Wilms tumor in this patient may be due to a trans effect from the maternal carrier in this SGBS kindred.
Li et al. (2001) performed GPC3 deletion screening on 80 male patients with somatic overgrowth in the following categories: 19 with Simpson-Golabi-Behmel syndrome, 26 with possible SGBS, and 35 with Beckwith-Wiedemann syndrome. Using exon-specific PCR and Southern blot analysis, 7 GPC3 deletions were identified, 6 from the SGBS category and 1 from the possible SGBS category. None of the patients with Beckwith-Wiedemann syndrome had GPC3 deletions. GPC3 deletions were identified in 2 patients from families published previously as having other overgrowth syndromes: one with a diagnosis of Sotos syndrome (117550) and the other with Perlman syndrome with nephroblastomatosis. One patient developed hepatoblastoma, which had not previously been described in SGBS. Direct sequencing of all GPC3 exons of the 13 SGBS patients without deletions failed to identify any further mutations, suggesting that alternative silencing mechanisms and/or other genes may be involved in the pathogenesis of SGBS.
Rodriguez-Criado et al. (2005) described 2 molecularly confirmed families with SGBS. All patients had typical manifestations of SGBS, including some female relatives who had minor manifestations. Some patients had novel findings such as a deep V-shaped sella turcica and 6 lumbar vertebrae. Molecular studies in affected patients showed a deletion of exon 6 of the GPC3 gene in family 1 (300037.0008) and an intronic mutation in the GPC3 gene in family 2 (300037.0009).
Romanelli et al. (2007) reported 2 brothers with SGBS caused by a truncating mutation in the GPC3 gene (300037.0010). The mutation was not present in the mother, indicating germinal mosaicism.
Sakazume et al. (2007) identified mutations in the GPC3 gene in 7 Japanese boys with SGBS. One of the boys had an affected younger brother. All the mutations were predicted to resulted in complete loss of function. Only 1 patient had a large deletion, and there were 5 nonsense and 1 frameshift mutation. There were no apparent genotype/phenotype correlations.
### GPC4 Gene
Veugelers et al. (1998) found that 1 of the SGBS patients reported by Pilia et al. (1996) had a deletion of the entire GPC4 gene (300168) as well as deletion of the last 2 exons of GPC3.
In 2 males with SGBS who were part of the original family reported by Golabi and Rosen (1984), Waterson et al. (2010) found no mutations in exons or intron/exon boundaries of the GPC3 gene. However, multiple ligation-dependent probe amplification (MLPA) analysis identified a duplication of exons 1 through 9 of the GPC4 gene. Dosage studies in 1 of the patients confirmed the duplication, whereas dosage of the GPC3 gene was normal. The 2 genes are closely linked and encode similar proteoglycans. Waterson et al. (2010) suggested that the duplication may affect, and possibly decrease, expression of the GPC3 gene, thus leading to the phenotype. The phenotype of the 2 boys was consistent with SGBS, with features of an overgrowth syndrome, genitourinary anomalies, vertebral anomalies, clefting, and coarse facial features. Waterson et al. (2010) concluded that GPC4 testing should be considered in patients who have no identifiable GPC3 mutations.
History
Gurrieri et al. (2011) reported the discovery of what is believed to be the first case of SGBS on record, an infant boy born around 1940. The infant was ascertained through a male Italian proband, born in 2001, who presented with classic features of the disorder and was subsequently found to carry a truncating mutation in the GPC3 gene. Family history showed that the proband's mother, who was of above average height and developed a low-grade ovarian tumor at age 22 years, also carried the mutation in the heterozygous state. The proband's maternal grandmother also carried the mutation. Familial recollections revealed that the proband's maternal great-grandmother had 2 male macrosomic children who died in the neonatal period. One of these infants was placed in a jar in formaldehyde in the Ospedale Carlo Forlanini anatomical museum in Rome. This infant was located, noted to be macrosomic, and a skin biopsy confirmed that this boy was a carrier of the same truncating mutation found in other family members.
INHERITANCE \- X-linked recessive GROWTH Height \- Tall stature \- Birth length greater than 97th percentile Weight \- Birth weight greater than 97th percentile Other \- Birth head circumference greater than 97th percentile HEAD & NECK Head \- Macrocephaly Face \- Coarse facies Ears \- Preauricular pits \- Preauricular tags \- Hearing loss Eyes \- Downslanting palpebral fissures \- Hypertelorism \- Epicanthal folds Nose \- Broad flat nasal bridge \- Short nose \- Upturned nose Mouth \- Macrostomia \- Macroglossia \- Midline groove of lower lip \- Broad secondary alveolar ridge \- Submucous cleft lip \- Cleft palate Teeth \- Dental malocclusion CARDIOVASCULAR Heart \- Cardiac conduction defects \- Ventricular septal defect \- Pulmonic stenosis \- Cardiomyopathy Vascular \- Transposition of great vessels \- Patent ductus arteriosus RESPIRATORY Lung \- Lung segmentation defects CHEST Ribs Sternum Clavicles & Scapulae \- Cervical ribs \- Pectus excavatum \- 13 pairs of ribs Breasts \- Supernumerary nipples Diaphragm \- Diaphragmatic hernia ABDOMEN External Features \- Umbilical hernias \- Diastasis recti Liver \- Hepatomegaly Pancreas \- Hyperplastic islets of Langerhans Spleen \- Polysplenia \- Splenomegaly Gastrointestinal \- Intestinal malrotation \- Meckel diverticulum GENITOURINARY External Genitalia (Male) \- Hypospadias \- Inguinal hernia Internal Genitalia (Male) \- Cryptorchidism Kidneys \- Large kidneys \- Cystic kidneys \- Duplication of renal pelvis SKELETAL \- Advanced bone age Spine \- Vertebral segmentation defects \- Fusion of C2-C3 posterior elements \- Six lumbar vertebrae \- Sacral defects \- Coccygeal defects \- Scoliosis Pelvis \- Flared iliac wing \- Narrow sacroiliac notches in infancy Hands \- Short broad hands \- Postaxial polydactyly \- Syndactyly 2nd-3rd fingers \- Broad thumbs \- Distal phalangeal hypoplasia \- Two carpal ossification centers present at birth Feet \- Short broad feet \- Syndactyly 2nd-3rd toes \- Broad toes \- Clubfoot SKIN, NAILS, & HAIR Skin \- Coccygeal skin tags Nails \- Fingernail hypoplasia NEUROLOGIC Central Nervous System \- Development varies from normal to retarded \- Agenesis of corpus callosum \- Cerebellar vermis hypoplasia \- Hydrocephalus \- Hypotonia NEOPLASIA \- Embryonal tumors \- Wilms tumor PRENATAL MANIFESTATIONS \- Nuchal translucency Maternal \- Increased alpha-fetoprotein MOLECULAR BASIS \- Caused by mutation in the glypican 3 gene (GPC3, 300037.0001) ▲ 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
| SIMPSON-GOLABI-BEHMEL SYNDROME, TYPE 1 | c0796154 | 2,377 | omim | https://www.omim.org/entry/312870 | 2019-09-22T16:17:16 | {"doid": ["0060248"], "mesh": ["C537340"], "omim": ["312870"], "orphanet": ["373"], "synonyms": ["Alternative titles", "SGBS", "BULLDOG SYNDROME", "DYSPLASIA GIGANTISM SYNDROME, X-LINKED", "GOLABI-ROSEN SYNDROME", "SIMPSON DYSMORPHIA SYNDROME"], "genereviews": ["NBK1219", "NBK1294"]} |
A number sign (#) is used with this entry because this form of platelet-type bleeding disorder (BDPLT11) can be caused by compound heterozygous mutation in the GP6 gene (605546) on chromosome 19q13.
Description
Platelet-type bleeding disorder-11 is an autosomal recessive mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen (summary by Dumont et al., 2009).
Clinical Features
Dumont et al. (2009) reported a 10-year-old girl with a history of easy bruising since infancy. Laboratory studies showed a prolonged bleeding time and failure of platelet activation and aggregation in response to collagen. Platelet response to ADP, arachidonic acid, and ristocetin was normal. Flow cytometric analysis of platelets showed an incomplete deficiency of glycoprotein VI, and the capacity of the patient's platelets to form thrombi on collagen in flow conditions was strongly impaired, with a 43% decreased surface coverage compared to control. There was also a marked defect in collagen-activated platelet-catalyzed thrombin generation.
Hermans et al. (2009) reported a 31-year-old woman with ecchymoses, epistaxis, several posttraumatic and postsurgery bleeding complications since childhood, and menorrhagia. Laboratory studies showed normal platelet numbers and morphology, but absent platelet activation and aggregation response to collagen. There was also increased adhesion of single platelets, likely due to other receptors. Flow cytometric analysis showed absent GP VI expression on platelets, whereas immunoblot analysis showed reduced but not absent GP VI expression.
Molecular Genetics
In a 10-year-old girl with mild platelet-type bleeding disorder-11, Dumont et al. (2009) identified compound heterozygosity for 2 mutations in the GP6 gene (605546.0001-605546.0002). Hermans et al. (2009) identified compound heterozygous GP6 mutations (605546.0003-605546.0004) in a woman with a mild bleeding disorder since childhood.
INHERITANCE \- Autosomal recessive HEAD & NECK Nose \- Epistaxis SKIN, NAILS, & HAIR Skin \- Ecchymoses \- Easy bruising HEMATOLOGY \- Bleeding, mild \- Menorrhagia \- Postsurgical bleeding \- Normal platelet morphology \- Prolonged bleeding time \- Decreased platelet expression of GP6 \- Defective platelet activation and aggregation in response to collagen \- Defective platelet binding to collagen MISCELLANEOUS \- Onset in infancy \- Variable severity MOLECULAR BASIS \- Caused by mutation in the platelet glycoprotein VI gene (GP6, 605546.0001 ) ▲ 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
| BLEEDING DISORDER, PLATELET-TYPE, 11 | c3280120 | 2,378 | omim | https://www.omim.org/entry/614201 | 2019-09-22T15:56:11 | {"doid": ["0111057"], "omim": ["614201"], "orphanet": ["98885", "73271"], "synonyms": ["Alternative titles", "GP VI DEFICIENCY", "GLYCOPROTEIN VI DEFICIENCY"]} |
3q29 microdeletion syndrome
Other names3qter deletion, Monosomy 3q29
Chromosome 3 is associated with this condition
3q29 microdeletion syndrome is a rare genetic disorder resulting from the deletion of a segment of chromosome 3. This syndrome was first described in 2005.[1][2]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Research
* 4 References
* 5 External links
## Presentation[edit]
The clinical phenotype of 3q29 microdeletion syndrome is variable. Clinical features can include mild/moderate intellectual disability with mildly dysmorphic facial features (long and narrow face, short philtrum and a high nasal bridge). Of the 6 reported patients, additional features including autism, ataxia, chest-wall deformity and long, tapering fingers were found in at least two patients.[1] A review of 14 children with interstitial deletions of 3q29, found 11 who had the common recurrent 1.6Mb deletion and displayed mental retardation and microcephaly.[3]
The variability of phenotype is underscored by the report on a 6 and 9/12 year-old male patient with a de novo chromosome 3q29 microdeletion identified by BAC array comparative genomic hybridization assay (aCGH), with accompanying normal 46,XY high-resolution chromosome analysis. The patient has language-based learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder (ADHD) of the inattentive type. He also displays some other features previously associated with chromosome 3q29 microdeletion such as an elongated face, long fingers, and joint laxity. Most notably the patient, per formal IQ testing, was not found to have frank intellectual disability as has been previously reported among patients with chromosome 3q29 terminal deletion, but rather the patient has demonstrated an average full-scale IQ result. This report further expands the phenotypic spectrum to include the possibility of normal intelligence as corroborated by formal, longitudinal psycho-educational testing.[4]
The presence of two homologous low copy repeats either side of the deletion break-point suggests that non-allelic homologous recombination is the likely mechanism underlying this syndrome.
## Genetics[edit]
The microdeletion, around 1.6 million base pairs, in length and encompasses 5 known genes and 17 uncharacterised transcripts. These include transferrin receptor, choline-phosphate cytidylyltransferase A, RNF168, serine/threonine-protein kinase, nuclear cap-binding protein complex, melanotransferrin, DLG1 and D-beta-hydroxybutyrate dehydrogenase
## Research[edit]
Research on the risk for developing schizophrenia in Ashkenazi Jews and other populations showed that 3q29 microdeletion syndrome leads to a significant higher rate of schizophrenia.[5] In addition, a deletion at 3q29 was found to confer a striking increase to the odds of developing schizophrenia in a study of copy number variants and their effect on that disease.[6]
## References[edit]
1. ^ a b Willatt L, Cox J, Barber J, et al. (July 2005). "3q29 Microdeletion Syndrome: Clinical and Molecular Characterization of a New Syndrome". Am. J. Hum. Genet. 77 (1): 154–60. doi:10.1086/431653. PMC 1226188. PMID 15918153.
2. ^ Koochek M (2006). "Clinical and molecular characterization of a new syndrome: the case of 3q29 microdeletion syndrome". Clin. Genet. 69 (2): 121–3. doi:10.1111/j.1399-0004.2006.00570c.x. Archived from the original on 2013-01-05.
3. ^ Ballif BC, Theisen A, Coppinger J, Gowans GC, Hersh JH, Madan-Khetarpal S, Schmidt KR, Tervo R, Escobar LF, Friedrich CA, McDonald M, Campbell L, Ming JE, Zackai EH, Bejjani BA, Shaffer LG (2008). "Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication". Mol Cytogenet. 1: 8. doi:10.1186/1755-8166-1-8. PMC 2408925. PMID 18471269.
4. ^ Cobb W, Anderson A, Turner C, Hoffman RD, Schonberg S, Levin SW (2010). "1.3 Mb de novo deletion in chromosome band 3q29 associated with normal intelligence in a child". Eur J Med Genet. 53 (6): 415–8. doi:10.1016/j.ejmg.2010.08.009. PMID 20832509.
5. ^ Mulle JG, Dodd AF, McGrath JA, Wolyniec PS, Mitchell AA, Shetty AC, Sobreira NL, Valle D, Rudd MK, Satten G, Cutler DJ, Pulver AE, Warren ST (August 2010). "Microdeletions of 3q29 confer high risk for schizophrenia". Am. J. Hum. Genet. 87 (2): 229–36. doi:10.1016/j.ajhg.2010.07.013. PMC 2917706. PMID 20691406.
6. ^ Rees E, Walters JT, Georgieva L, Isles AR, Chambert KD, Richards AL, Mahoney-Davies G, Legge SE, Moran JL, McCarroll SA, O'Donovan MC, Owen MJ, Kirov G (February 2014). "Analysis of copy number variations at 15 schizophrenia-associated loci". Br J Psychiatry. 204 (2): 108–14. doi:10.1192/bjp.bp.113.131052. PMC 3909838. PMID 24311552.
## External links[edit]
Classification
D
* ICD-10: Q93.5
* OMIM: 609425
* MeSH: C567184 C567184, C567184
External resources
* Orphanet: 65286
* DECIPHER database entry for 3q29 microdeletion syndrome
* 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
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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
| 3q29 microdeletion syndrome | c2674949 | 2,379 | wikipedia | https://en.wikipedia.org/wiki/3q29_microdeletion_syndrome | 2021-01-18T18:51:46 | {"gard": ["11974"], "mesh": ["C567184"], "umls": ["C2674949"], "orphanet": ["65286"], "wikidata": ["Q4636618"]} |
T-B- severe combined immunodeficiency (SCID; see this term) is a group of rare monogenic primary immunodeficiency disorders characterized by a lack of functional peripheral T and B lymphocytes, resulting in recurrent early-onset severe respiratory viral, bacterial or fungal infections, diarrhea and failure to thrive. Hypersensitivity to ionizing radiation is a characteristic feature of some of its sub-types.
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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
| T-B- severe combined immunodeficiency | None | 2,380 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=317419 | 2021-01-23T17:54:36 | {"icd-10": ["D81.1"], "synonyms": ["T-B- SCID"]} |
A number sign (#) is used with this entry because congenital dyserythropoietic anemia type IV (CDAN4) is caused by heterozygous mutation in the KLF1 gene (600599), which encodes a transcriptional activator, on chromosome 19p13.
Description
Congenital dyserythropoietic anemia type IV is an autosomal dominant inherited red blood cell disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDAN4 also have increased levels of fetal hemoglobin (summary by Arnaud et al., 2010).
For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see CDAN1 (224120).
Clinical Features
Wickramasinghe et al. (1991) described an 8-year-old Danish girl who was severely anemic and hydropic at birth due to a novel form of congenital dyserythropoietic anemia. She had a moderate normochromic anemia, increased levels of fetal hemoglobin (HbF) at 50%, increased reticulocyte count, and hyperbilirubinemia. Bone marrow smear showed intense normoblastic erythroid hyperplasia with morphologic evidence of dyserythropoiesis; the most common dysplastic features were basophilic stippling of polychromatic erythroblasts and erythrocytes, and marked abnormalities of nuclear shape in polychromatic erythroblasts. Electron microscopic studies showed that some polychromatic erythroblasts and several erythrocytes contained inclusions which were rounded, elongated, or irregular. There appeared to be a prolongation of, or an arrest at, the polychromatic erythroblast phase. Further studies of this patient showed that she had persistent embryonic and fetal hemoglobin (Tang et al., 1993), and absent red cell expression of CD44 (107269) (Parsons et al., 1994). The patient also had a unique blood group phenotype: In(a-b-), Co(a-b-). Agre et al. (1994) showed that the red cells from this patient contained less than 10% of the normal level of AQP1 (107776) and had remarkably low osmotic water permeability, but no mutation was identified in the AQP1 gene. The characteristics of CDA in this patient were different from those of the 3 other types of CDA. The CD44 and AQP1 deficiencies were not thought to represent primary defects.
Arnaud et al. (2010) reported an infant boy, born at 28 weeks' gestation due to acute fetal distress, with congenital dyserythropoietic anemia. Hydrops fetalis-associated anemia had been detected at 23 weeks' gestation and treated with 2 intrauterine transfusions. At birth, he had severe hyperbilirubinemia, hepatomegaly, hypertrophic cardiomyopathy, and several dysmorphic features, including micropenis, hypospadias, large anterior fontanel, and hypertelorism. He required transfusions every 2 to 3 weeks until age 4 years when splenectomy was performed. He became transfusion independent after splenectomy and showed short stature at age 13 years. Bone marrow smear showed marked hyperplasia of the erythroid lineage, leading to a diagnosis of CDA, but the dysplastic changes in the erythroblasts did not clearly fit any established classification. Peripheral blood smear showed very large numbers of nucleated red blood cells, suggesting a failure of enucleation and a defect in terminal erythroid differentiation. Electron microscopy showed various ultrastructural abnormalities, including atypical cytoplasmic inclusions and enlarged nuclear pores. Flow cytometry showed a combined deficiency of CD44 and AQP1 expression limited to erythrocytes. Isoelectric focusing showed large amounts of fetal hemoglobin, indicating a dysregulation of globin gene expression (see, e.g., HBB, 141900 and HBG1, 142200).
Molecular Genetics
In 2 unrelated patients with congenital dyserythropoietic anemia type IV, one of whom was the patient reported by Wickramasinghe et al. (1991), Arnaud et al. (2010) identified a heterozygous de novo mutation in the KLF1 gene (E325K; 600599.0006). The mutant protein showed markedly decreased transcriptional activity toward CD44 and AQP1 compared to wildtype, consistent with the clinical findings. The mutant KLF1 protein also showed a dominant-negative effect. The findings indicated that the KLF1 gene plays a critical role in the regulation of several genes during erythropoiesis, and that dysregulation of certain gene targets can result in dyserythropoiesis.
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy (1 patient) ABDOMEN Liver \- Hepatomegaly Spleen \- Splenomegaly HEMATOLOGY \- Ineffective erythropoiesis \- Anemia \- Nucleated peripheral red cells \- Circulating orthochromatic erythroblasts \- Increased reticulocyte count \- Decreased expression of CD44 and AQP1 on red cells \- Increased fetal hemoglobin \- Bone marrow smear shows erythroid hyperplasia \- Erythroblasts show atypical cytoplasmic inclusions PRENATAL MANIFESTATIONS Amniotic Fluid \- Hydrops fetalis LABORATORY ABNORMALITIES \- Hyperbilirubinemia MISCELLANEOUS \- De novo mutation \- Onset in utero \- Two unrelated patients have been reported (last curated December 2010) MOLECULAR BASIS \- Caused by mutation in the Krupple-like factor 1 gene (KLF1, 600599.0006 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE IV | c3150926 | 2,381 | omim | https://www.omim.org/entry/613673 | 2019-09-22T15:58:02 | {"doid": ["1338"], "omim": ["613673"], "orphanet": ["293825"], "synonyms": ["CDA type 4", "CDA due to KLF1 mutation", "CDA, TYPE IV", "CDA type IV", "Congenital dyserythropoietic anemia type 4", "CDA IV", "Alternative titles", "CDAN4", "Congenital dyserythropoietic anemia due to KLF1 mutation"]} |
Pierquin et al. (1991) reported the cases of 2 unrelated children with similar clinical features, particularly facial dysmorphism and multiple joint dislocations, suggesting the diagnosis of Larsen syndrome (150250). Both carried an inherited unbalanced translocation resulting in partial trisomy 1q and partial monosomy 6p. Skin collagen showed a decreased alpha-1/alpha-2 chain ratio in type I collagen (see 120150). Pierquin et al. (1991) suggested that both patients had a mutation in a gene involved in collagen production which is located either on chromosome 1q or, more likely, on 6p.
Chromosome 6 likewise came under suspicion in the family reported by James et al. (2003). The proband, a child with Larsen-like features and severe developmental delay, had an unbalanced translocation resulting in a distal 6p deletion and proximal trisomy 10q. The father and an unaffected older brother had a balanced form of the translocation, t(6;10)(p25;q25.2). James et al. (2003) suggested that the 2 translocation patients reported by Pierquin et al. (1991) and their patient supported the possibility of a locus responsible for a Larsen-like phenotype determined by genes in the distal 6p region. Their case had a more distal breakpoint, refining the potential critical region.
INHERITANCE \- Isolated cases GROWTH Height \- Short stature HEAD & NECK Head \- Macrocephaly \- Brachycephaly \- Large anterior fontanel Face \- Flat face \- Prominent forehead Ears \- Low-set ears \- Conductive hearing loss \- Recurrent episodes of otitis media Eyes \- Hypertelorism Nose \- Absent nasal bridge Mouth \- Cleft palate Teeth \- Malocclusion SKELETAL \- Joint laxity (hip, knee, shoulder, wrist, fingers) \- Joint dislocations \- Delayed bone age Spine \- Kyphoscoliosis Hands \- Cylindrical fingers \- Clinodactyly (4th and 5th fingers) Feet \- Clubfoot \- Double calcaneal ossification center NEUROLOGIC \- Hypotonia Central Nervous System \- Developmental delay LABORATORY ABNORMALITIES \- Abnormal karyotype in 3 patients involving distal 6p ▲ 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
| LARSEN-LIKE SYNDROME | c1837884 | 2,382 | omim | https://www.omim.org/entry/608545 | 2019-09-22T16:07:40 | {"mesh": ["C563914"], "omim": ["608545"], "orphanet": ["2370"], "synonyms": ["Alternative titles", "LRSL"]} |
Dyschromatosis universalis hereditaria
SpecialtyDermatology
Dyschromatosis universalis hereditaria is a rare genodermatosis characterized by reticulate hyper- and hypo- pigmentated macules in a generalized distribution.[1]:856
Both autosomal dominant and recessive inheritance have been reported with the disorder.[2]
It has been associated with mutations in genes SASH1 and ABCB6.
## 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. ^ Stuhrmann M, Hennies HC, Bukhari IA, Brakensiek K, Nürnberg G, Becker C, Huebener J, Miranda MC, Frye-Boukhriss H, Knothe S, Schmidtke J, El-Harith EH (June 2008). "Dyschromatosis universalis hereditaria: evidence for autosomal recessive inheritance and identification of a new locus on chromosome 12q21-q23". Clinical Genetics. 73 (6): 566–572. doi:10.1111/j.1399-0004.2008.01000.x. PMID 18462451. S2CID 9623609.
## External links[edit]
Classification
D
* OMIM: 127500
* MeSH: C535730
* DiseasesDB: 32816
External resources
* Orphanet: 241
* Dyschromatosis universalis hereditaria: Two cases, Dermatology Online Journal.
* v
* t
* e
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
* Ichthyosis vulgaris
AR
* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis
* Lamellar ichthyosis
* Harlequin-type ichthyosis
* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome
XR
* X-linked ichthyosis
Ungrouped
* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix
EB
and related
* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP
* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA
* DEB
* DDEB
* RDEB
* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome
Ectodermal dysplasia
* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome
Elastic/Connective
* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome
Hyperkeratosis/
keratinopathy
PPK
* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease
* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II
* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma
* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID
Other
* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome
* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris
Other
* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey
see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder
Developmental
anomalies
Midline
* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii
Nevus
* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae
Other/ungrouped
* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation
* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark
This Genodermatoses 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
| Dyschromatosis universalis hereditaria | c1306229 | 2,383 | wikipedia | https://en.wikipedia.org/wiki/Dyschromatosis_universalis_hereditaria | 2021-01-18T18:53:31 | {"gard": ["1996"], "mesh": ["C535730"], "umls": ["C1306229"], "orphanet": ["241"], "wikidata": ["Q5319369"]} |
Partial or complete wasting away of a part of the body
For the American thrash metal band, see Atrophy (band).
Atrophy
Mouse (right) with spinal muscular atrophy
SpecialtyPathology
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, excessive amount of apoptosis of cells, and disuse or lack of exercise or disease intrinsic to the tissue itself. In medical practice, hormonal and nerve inputs that maintain an organ or body part are said to have trophic effects. A diminished muscular trophic condition is designated as atrophy. Atrophy is reduction in size of cell, organ or tissue, after attaining its normal mature growth. In contrast, hypoplasia is the reduction in size of a cell, organ, or tissue that has not attained normal maturity.
Atrophy is the general physiological process of reabsorption and breakdown of tissues, involving apoptosis. When it occurs as a result of disease or loss of trophic support because of other diseases, it is termed pathological atrophy, although it can be a part of normal body development and homeostasis as well.
## Contents
* 1 Normal development
* 2 Muscle atrophies
* 3 Dystrophies, myositis, and motor neuron conditions
* 4 Gland atrophy
* 5 Vaginal atrophy
* 6 Research
* 7 See also
* 8 References
* 9 External links
## Normal development[edit]
-plasia and -trophy
* Anaplasia (structural differentiation loss within a cell or group of cells).
* Aplasia (organ or part of organ missing)
* Desmoplasia (connective tissue growth)
* Dysplasia (change in cell or tissue phenotype)
* Hyperplasia (proliferation of cells)
* Hypoplasia (congenital below-average number of cells, especially when inadequate)
* Metaplasia (conversion in cell type)
* Neoplasia (abnormal proliferation)
* Prosoplasia (development of new cell function)
* Abiotrophy (loss in vitality of organ or tissue)
* Atrophy (reduced functionality of an organ, with decrease in the number or volume of cells)
* Hypertrophy (increase in the volume of cells or tissues)
* Hypotrophy (decrease in the volume of cells or tissues)
* Dystrophy (any degenerative disorder resulting from improper or faulty nutrition)
* v
* t
* e
Examples of atrophy as part of normal development include shrinking and the involution of the thymus in early childhood, and the tonsils in adolescence. In old age, effects include, but are not limited to, loss of teeth, hair, thinning of skin that creates wrinkles, weakening of muscles, loss of weight in organs and sluggish mental activity.[1]
## Muscle atrophies[edit]
Main article: Muscle atrophy
Disuse atrophy of muscles and bones, with loss of mass and strength, can occur after prolonged immobility, such as extended bedrest, or having a body part in a cast (living in darkness for the eye, bedridden for the legs etc.). This type of atrophy can usually be reversed with exercise unless severe.
There are many diseases and conditions which cause atrophy of muscle mass. For example, diseases such as cancer and AIDS induce a body wasting syndrome called cachexia, which is notable for the severe muscle atrophy seen. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart failure and liver disease.
During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called sarcopenia, and may be distinct from atrophy in its pathophysiology. While the exact cause of sarcopenia is unknown, it may be induced by a combination of a gradual failure in the satellite cells which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.[2]
## Dystrophies, myositis, and motor neuron conditions[edit]
Pathologic atrophy of muscles can occur with diseases of the motor nerves or diseases of the muscle tissue itself. Examples of atrophying nerve diseases include Charcot-Marie-Tooth disease, poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and Guillain–Barré syndrome. Examples of atrophying muscle diseases include muscular dystrophy, myotonia congenita, and myotonic dystrophy.
Changes in Na+ channel isoform expression and spontaneous activity in muscle called fibrillation can also result in muscle atrophy.
A flail limb is a medical term which refers to an extremity in which the primary nerve has been severed, resulting in complete lack of mobility and sensation. The muscles soon wither away from atrophy.
## Gland atrophy[edit]
The adrenal glands atrophy during prolonged use of exogenous glucocorticoids like prednisone. Atrophy of the breasts can occur with prolonged estrogen reduction, as with anorexia nervosa or menopause. Testicular atrophy can occur with prolonged use of enough exogenous sex steroids (either androgen or estrogen) to reduce gonadotropin secretion.
## Vaginal atrophy[edit]
In post-menopausal women, the walls of the vagina become thinner (atrophic vaginitis). The mechanism for the age-related condition is not yet clear, though there are theories that the effect is caused by decreases in estrogen levels.[3] This atrophy, and that of the breasts concurrently, is consistent with the homeostatic (normal development) role of atrophy in general, as after menopause the body has no further functional biological need to maintain the reproductive system which it has permanently shut down.
## Research[edit]
One drug in test seemed to prevent the type of muscle loss that occurs in immobile, bedridden patients.[4] Testing on mice showed that it blocked the activity of a protein present in the muscle that is involved in muscle atrophy.[5] However, the drug's long-term effect on the heart precludes its routine use in humans, and other drugs are being sought.[4]
## See also[edit]
* Olivopontocerebellar atrophy
* Optic atrophy
* Spinomuscular atrophy
* Hypertrophy
* List of biological development disorders
## References[edit]
1. ^ W. T. Councilman (1913). "Chapter Two". Disease and Its Causes. New York Henry Holt and Company London Williams and Norgate The University Press, Cambridge, U.S.A.
2. ^ Campellone, Joseph V. (2007-05-22). "Muscle atrophy". MedlinePlus. Archived from the original on 13 October 2007. Retrieved 2007-10-02.
3. ^ "Types of Atrophy". Archived from the original on 28 September 2007. Retrieved 2007-10-02.
4. ^ a b "Drug could stop muscle wasting'". NetDoctor.co.uk. 2006-05-25. Archived from the original on 2007-09-11. Retrieved 2006-05-27.
5. ^ Wang X, Hockerman GH, Green Iii HW, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL (May 24, 2006). "Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway". FASEB J. 20 (9): 1531–3. doi:10.1096/fj.05-5350fje. PMID 16723379.
## External links[edit]
Classification
D
* MeSH: D001284
* SNOMED CT: 13331008
* v
* t
* e
Pathology
Principles of pathology
* Disease
* Infection
* Neoplasia
* Cause
* Pathogenesis
* Hemodynamics
* Ischemia
* Inflammation
* Cell damage
* Wound healing
Cellular adaptation
Atrophy
Hypertrophy
Hyperplasia
Dysplasia
Metaplasia
Squamous
Glandular
Cell death
Necrosis
Coagulative necrosis
Liquefactive necrosis
Gangrenous necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
Myocytolysis
Programmed cell death
Apoptosis
Pyknosis
Karyorrhexis
Karyolysis
Accumulations
pigment
Hemosiderin
Lipochrome/Lipofuscin
Melanin
Steatosis
Anatomical pathology
* Surgical pathology
* Cytopathology
* Autopsy
* Molecular pathology
* Forensic pathology
* Oral and maxillofacial pathology
* Gross examination
* Histopathology
* Immunohistochemistry
* Electron microscopy
* Immunofluorescence
* Fluorescence in situ hybridization
Clinical pathology
* Clinical chemistry
* Hematopathology
* Transfusion medicine
* Medical microbiology
* Diagnostic immunology
* Immunopathology
* Enzyme assay
* Mass spectrometry
* Chromatography
* Flow cytometry
* Blood bank
* Microbiological culture
* Serology
* v
* t
* e
Skin lesion terminology
Macroscopic
Primary lesions
* flat
* Macule
* Patch
* elevated
* Papule
* Nodule
* Plaque
* fluid
* Vesicle
* Bulla
* Pustule
* Ulcer
* Erosion
* Telangiectasia
* Special initial lesions : Burrow
* Tunnel
* Comedo
* Scutulum
* Target lesion
* Herald patch
* Wheal
Secondary lesions
* Scale
* Crust
* Lichenification
* Excoriation
* Induration
* Atrophy
Microscopic
* keratin: Hyperkeratosis
* Parakeratosis
* Dyskeratosis
* Hypergranulosis
* Acanthosis
* Papillomatosis
* Acantholysis
* Spongiosis
* Hydropic swelling
* Exocytosis
* Vacuolization
* Erosion
* Ulceration
* Lentiginous
*[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
| Atrophy | c0333641 | 2,384 | wikipedia | https://en.wikipedia.org/wiki/Atrophy | 2021-01-18T18:32:03 | {"mesh": ["D001284"], "wikidata": ["Q194520"]} |
Hemoglobin Constant Spring is a variant of hemoglobin in which a mutation in the alpha globin gene produces an alpha globin chain that is abnormally long. It is the most common nondeletional alpha-thalassemia mutation associated with hemoglobin H disease.[1] The quantity of hemoglobin in the cells is low because the messenger RNA is unstable and some is degraded prior to protein synthesis. Another reason is that the Constant Spring alpha chain protein is itself unstable. The result is a thalassemic phenotype.[2][3]
Hemoglobin Constant Spring is renamed after Constant Spring district in Jamaica.[4]
## See also[edit]
* Hemoglobin variants
* Hemoglobinopathy
* Thalassemia
## References[edit]
1. ^ What is Thalassemia? Hemoglobin H Disease and its Variants
2. ^ Hemoglobinopathiesm(Hemoglobin Disorders)
3. ^ Schrier, SL; Bunyaratvej, A; Khuhapinant, A; Fucharoen, S; Aljurf, M; Snyder, LM; Keifer, CR; Ma, L; Mohandas, N (1997). "The unusual pathobiology of hemoglobin constant spring red blood cells". Blood. 89: 1762–9. PMID 9057661.
4. ^ About Thalassemia
*[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
| Hemoglobin Constant Spring | c3891114 | 2,385 | wikipedia | https://en.wikipedia.org/wiki/Hemoglobin_Constant_Spring | 2021-01-18T18:59:43 | {"wikidata": ["Q28209257"]} |
## Summary
### Clinical characteristics.
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by mid-adult onset of recurrent ischemic stroke, cognitive decline progressing to dementia, a history of migraine with aura, mood disturbance, apathy, and diffuse white matter lesions and subcortical infarcts on neuroimaging.
### Diagnosis/testing.
The diagnosis of CADASIL is established in a proband either by identification of a heterozygous pathogenic variant in NOTCH3 by molecular genetic testing or, if molecular genetic testing is not definitive, by detection of characteristic findings by electron microscopy and immunohistochemistry of a skin biopsy.
### Management.
Treatment of manifestations: There is no treatment of proven efficacy for CADASIL. Standard supportive treatment for stroke; the effect of thrombolytic therapy for the treatment of stroke remains unknown. Migraine should be treated symptomatically. Standard treatment for psychiatric disturbance. Supportive care (practical help, emotional support, and counseling) is appropriate for affected individuals and their families.
Prevention of primary manifestations: Antiplatelet therapy may be considered for prevention of stroke/TIA, but efficacy has not been proven. Anticoagulants should be avoided if possible. Control of vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking). Prophylactic treatment of migraines, depending on the frequency.
Surveillance: Routine evaluation by a neurologist with expertise in CADASIL; consultation with a neuropsychiatrist if symptoms of depression, apathy, or psychiatric manifestations; consultation with other medical specialists (e.g., rehabilitation physician, clinical geneticist, physical therapist, and psychologist) as needed.
Agents to avoid: Thrombolytic therapy (intravenous thrombolysis) and oral anticoagulants probably increase the risk of intracerebral hemorrhage in individuals with CADASIL. These agents should therefore only be used carefully and on a case-by-case basis. Smoking increases the risk of stroke.
Pregnancy management: There may be an increased risk for neurologic events in pregnancy during and shortly after delivery (puerperium); transient neurologic events (migraine with aura) have most commonly been reported.
### Genetic counseling.
CADASIL is inherited in an autosomal dominant manner. Most affected individuals have an affected parent; de novo pathogenic variants appear to be rare. Each child of an affected person is at a 50% risk of inheriting the pathogenic variant and developing signs of the disease. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the pathogenic variant in the family is known.
## Diagnosis
There are no generally accepted diagnostic criteria for CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). A CADASIL diagnostic screening tool has been proposed by Pescini et al [2012], Mizuta et al [2017], and Bersano et al [2018].
### Suggestive Findings
CADASIL should be suspected in individuals with unexplained white matter hyperintensities and a family history of stroke and/or vascular dementia; however, lack of an apparent family history of CADASIL does not preclude the diagnosis (see Family history). The following clinical signs and neuroimaging findings can be observed in CADASIL.
Clinical signs
* Transient ischemic attacks and ischemic stroke
* Cognitive impairment, manifesting initially with executive dysfunction, with a concurrent stepwise deterioration due to recurrent strokes to vascular dementia
* Migraine with aura, with a mean age of onset of 30 years
* Psychiatric disturbances, most frequently mood disturbances and apathy
Brain imaging
* Symmetric and progressive white matter hyperintensities, often involving the anterior temporal lobes and external capsules
* Lacunes of presumed vascular origin
* Recent subcortical infarcts
* Dilated perivascular spaces, sometimes referred to as subcortical lacunar lesions
* Brain atrophy
* Cerebral microbleeds
Family history consistent with autosomal dominant inheritance is suggestive. Note, however, that lack of an apparent family history of CADASIL does not preclude the diagnosis, as affected family members may have been misdiagnosed [Razvi et al 2005a] and de novo cases have been described [Joutel et al 2000, Coto et al 2006].
### Establishing the Diagnosis
The diagnosis of CADASIL is established in a proband either by identification of a heterozygous pathogenic variant in NOTCH3 by molecular genetic testing (see Table 1) or, if molecular genetic testing is not definitive, by detection of characteristic findings by electron microscopy and immunohistochemistry of a skin biopsy.
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of CADASIL is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with recurrent stroke and/or dementia are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of CADASIL, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of NOTCH3 (to include, at a minimum, exons 2-24) detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.
Perform sequence analysis first. If a biallelic pathogenic variant is identified, consider gene-targeted deletion/duplication analysis to determine if an unidentified exon deletion or duplication is present.
Note: Biallelic NOTCH3 pathogenic variants have been described in individuals with CADASIL (see Genotype-Phenotype Correlations).
* A multigene panel that includes NOTCH3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other inherited disorders characterized by stroke and/or dementia, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in CADASIL
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Gene 1Test MethodProportion of Probands with a Pathogenic Variant 2 Detectable by This Method
NOTCH3Sequence analysis 3Estimated >95% 4
Gene-targeted deletion/duplication analysis 5Unknown 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\.
When all exons coding for epidermal growth factor-like repeats (see Molecular Genetics) are sequenced (exons 2-24) and stringent inclusion criteria are applied [Markus et al 2002, Peters et al 2005a]
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\.
Rutten et al [2013]
Skin biopsy. The diagnosis can be confirmed by ultrastructural analysis of small arterioles obtained, for example, by skin biopsy [Goebel et al 1997, Ruchoux & Maurage 1997]. Electron microscopy shows characteristic granular osmophilic material (GOM) within the vascular media close to vascular smooth muscle cells. The detection of GOM is considered pathognomonic for CADASIL, but the reported sensitivity is variable [Tikka et al 2009, Morroni et al 2013].
NOTCH3 immunostaining of a skin biopsy shows a positive granular NOTCH3 staining of the vessel wall [Joutel et al 2001, Oberstein 2003].
The combined analysis by electron microscopy and immunohistochemistry, when interpreted by an experienced (neuro)pathologist, usually allows for a conclusive CADASIL diagnosis [Rutten et al 2014].
## Clinical Characteristics
### Clinical Description
CADASIL is a disease of the small to medium-sized arteries, mainly affecting the brain. The presenting symptoms, age at onset, and disease progression in CADASIL are variable, both between and within families. The disease is characterized by five main symptoms: transient ischemic attacks and recurrent ischemic strokes; cognitive decline; migraine with aura; mood disturbance; and apathy.
Subcortical ischemic events. Transient ischemic attacks (TIAs) and stroke, the most frequent presentation, are found in approximately 85% of symptomatic individuals [Dichgans et al 1998]. Mean age at onset for ischemic episodes is 47 years (age range 20-70 years) [Opherk et al 2004].
Ischemic episodes typically present as a classic lacunar syndrome (pure motor stroke, ataxic hemiparesis/dysarthria-clumsy hand syndrome, pure sensory stroke, sensorimotor stroke), but other lacunar syndromes (brain stem or hemispheric) are also observed [Adib-Samii et al 2010]. Ischemic episodes are often recurrent, leading to severe disability with gait disturbance, urinary incontinence, and pseudobulbar palsy.
Strokes involving the territory of a large artery have occasionally been reported. However, whether these are coincidental observations, or whether (certain sub-populations of) individuals with CADASIL are at increased risk for large vessel stroke, is unclear [Choi et al 2013, Yin et al 2015, Kang & Kim 2015].
Cognitive deficits and dementia. Cognitive decline may start as early as age 35 years. Up to 75% of affected individuals develop dementia, often accompanied by apathy [Dichgans 2009, Reyes et al 2009].
The pattern of cognitive dysfunction is initially characterized by deficits in executive function (timed measures and measures of error monitoring), verbal fluency, and memory with benefit from clues [Peters et al 2005b]. Cognitive dysfunction is accompanied by a narrowing of the field of interest. In most cases, cognitive decline is slowly progressive, with some preservation of recognition and semantic memory, with additional stepwise deterioration. Visuospatial abilities and reasoning decline, especially after age 60. Cognitive decline becomes more apparent with aging and disease progression, ultimately leading to significant alterations in all cognitive domains at an older age [Buffon et al 2006]. Amberla et al [2004] observed deterioration of working memory and executive function in individuals with NOTCH3 pathogenic variants in the pre-stroke phase and inferred that cognitive decline may start insidiously before the onset of symptomatic ischemic episodes.
Migraine, when present, can be the first symptom of CADASIL. Migraine occurs in 30%-75% of individuals with CADASIL, with the first attack occurring at a mean age of 26-29 years [Adib-Samii et al 2010, Tan & Markus 2016, Guey et al 2016]. Eighty to ninety percent of those with migraine have migraine with aura [Guey et al 2016, Tan & Markus 2016]. Migraine auras are sometimes confused with transient ischemic symptoms, since aura may include focal neurologic deficits [Di Donato et al 2017]. Sixty percent of those with migraine with aura have experienced an atypical migraine attack: prolonged, basilar or hemiplegic aura, confusion, fever, or coma [Guey et al 2016].
Psychiatric disorders. In most CADASIL cohorts, psychiatric disturbances are described in about one third of individuals [Adib-Samii et al 2010]. The reported prevalence of psychiatric disturbances is variable: a small study in 23 Italian patients recorded a lifetime risk for depression of 74% and a lifetime risk for a manic episode of 26% [Valenti et al 2011], whereas in a Chinese cohort, psychiatric manifestations were recorded in only 7% of affected individuals [Wang et al 2011]. Apathy has been described in 40% of individuals [Reyes et al 2009]. The psychiatric manifestations vary from personality changes to severe depression. The pathogenesis of psychiatric disturbances in CADASIL is incompletely understood. Psychiatric problems as a presenting symptom of CADASIL have been described [Leyhe et al 2005, Nakamura et al 2005, Park et al 2014].
Reversible acute encephalopathy. Acute encephalopathy has been described in some individuals, with confusion, headache, pyrexia, seizures, and coma, sometimes leading to death [Adib-Samii et al 2010, Ragno et al 2013, Tan & Markus 2016]. Migraine with aura (especially confusional aura) is associated with increased risk of acute encephalopathy, suggesting that they may share pathophysiologic mechanisms [Tan & Markus 2016].
Epilepsy. Epilepsy occurs in 10% of individuals with CADASIL and presents in middle age, usually secondary to stroke [Haan et al 2007]. In a pooled analysis of previous published cases, three of 105 individuals with CADASIL had a seizure as the initial presenting symptom [Desmond et al 1999].
Pregnancy. It has been suggested that the risk for migraine with aura is increased during pregnancy, but especially during puerperium (the period between childbirth and the return of the uterus to its normal size) [Roine et al 2005]. Another study found no association between pregnancy and risk for neurologic events or problems during pregnancy [Donnini et al 2017]. See Pregnancy Management.
Other findings
* Cardiac. Controversy exists as to whether CADASIL is associated with cardiac involvement. In a study from The Netherlands, nearly 25% of individuals with CADASIL had a history of acute myocardial infarction (MI) and/or current pathologic Q-waves on electrocardiogram (ECG) [Lesnik Oberstein et al 2003]. This percentage was significantly higher than in controls without a heterozygous NOTCH3 pathogenic variant. However, another study of 23 individuals with CADASIL found no signs of previous MI on ECG [Cumurciuc et al 2006b]. Two studies have suggested an increased risk for arrhythmias, based on increased QT variability on ECG recording [Rufa et al 2007, Piccirillo et al 2008].
* Nerve. Nerve biopsies may demonstrate signs of axonal damage, demyelination, and ultrastructural changes of the endoneurial blood vessels [Schröder et al 2005, Sicurelli et al 2005, Lackovic et al 2012]. Punch skin biopsies from individuals with CADASIL showed cutaneous somatic and autonomic nerve involvement [Nolano et al 2016]. Clinically, however, there is no clear evidence that peripheral neuropathy is part of the CADASIL clinical spectrum [Kang et al 2009].
* Ocular. Subclinical retinal lesions are reported [Cumurciuc et al 2004, Haritoglou et al 2004]. Fundoscopy may reveal clinically silent retinal vascular abnormalities [Pretegiani et al 2013]. Optical coherence tomography imaging techniques may show reduced subfoveal choroidal thickness, retinal arterial luminal narrowing, retinal venous luminal enlargement, and reduced vessel density of the deep retinal plexus [Alten et al 2014, Fang et al 2017, Nelis et al 2018].
* Renal. NOTCH3 accumulation and granular osmophilic material (GOM) are also detected in renal arteries, and stenosis of renal arteries has been described [Ragno et al 2012, Lorenzi et al 2017]. Although no large-scale studies have been published regarding kidney function in individuals with CADASIL, to date there is no evidence that kidney function is affected [Bergmann et al 1996].
Long-term prognosis and causes of death. Onset of symptoms and overall survival may vary based on the type of pathogenic variant and its location within NOTCH3 (see Genotype-Phenotype Correlations).
Data on the long-term prognosis in CADASIL come from a large study of 411 individuals [Opherk et al 2004], which found that the median age at onset of inability to walk without assistance was approximately 60 years and the median age at which individuals became bedridden was 64 years. The median age at death was 68 years with a more rapid disease progression in men than in women. Pneumonia was the most frequent cause of death, followed by sudden unexpected death and asphyxia. In the final stages of disease, 78% of individuals were completely dependent and 63% were confined to bed.
The median survival time of men was significantly shorter than expected from German life tables, whereas the median survival time of women was not significantly reduced. The reason for this difference is not known; possible explanations include sex hormones, sex differences in risk factor control, medical management, social support, and socioeconomic factors.
Brain imaging. Imaging abnormalities in CADASIL evolve as the disease progresses [van den Boom et al 2003, Singhal et al 2005, Liem et al 2008a]:
* In individuals age 20-30 years, distinctive white matter hyperintensities often first appear in the anterior temporal lobes, when the rest of the white matter, except for periventricular caps, appears unaffected [Oberstein 2003, van den Boom et al 2003].
* In the course of the disease, the load of white matter hyperintensity lesions increases, eventually coalescing to the point where, in some elderly individuals, normal-appearing white matter is barely distinguishable [Chabriat et al 1998].
* White matter hyperintensities in the temporal lobe and external capsule are characteristic for CADASIL but not always present [O’Sullivan et al 2001, Markus et al 2002]. Involvement of the anterior temporal lobe is highly suggestive for CADASIL; this finding, however, is not sensitive or specific for the diagnosis of CADASIL [Sureka &Jakkani 2012].
* In symptomatic individuals, white matter hyperintensities are symmetrically distributed and located in the periventricular and deep white matter. Within the white matter, the frontal lobe is the site with the highest lesion load, followed by the temporal and parietal lobes [Auer et al 2001, O'Sullivan et al 2001].
* The majority of lacunes develop at the edge of white matter hyperintensities and proximal to white matter hyperintensities along the course of perforating vessels supplying the respective brain region [Duering et al 2013].
* Brain atrophy appears to result from accumulation of lacunes and widespread microstructural alterations within the brain [Jouvent et al 2007].
* Lacunes and brain atrophy are strongly correlated with clinical severity and clinical worsening in individuals with CADASIL [Ling et al 2018, Jouvent et al 2016].
* Dilated perivascular spaces are found in approximately 70%-80% of affected individuals [van Den Boom et al 2002, Cumurciuc et al 2006a, Yao et al 2014].
* Cerebral microbleeds (CMB) are reported in approximately one third of affected individuals [Puy et al 2017, Nannucci et al 2018]. Cerebral microbleeds do not have a clear predominant location in individuals with CADASIL. In a study of 125 affected individuals, cerebral microbleeds were present in 34%. Of these, 29% had CMB in the deep subcortical region (most frequently in the thalamus), 22% in the lobar region (especially the temporal lobe), and 18% in the infratentorial region [Nannucci et al 2018].
Other imaging studies. Positron emission tomography, transcranial Doppler sonography, and perfusion MRI may show decreased cerebral blood flow, decreased cerebral blood volume, impaired cerebral metabolism, decreased vasoreactivity, and altered neurovascular coupling [Tatsch et al 2003, Tuominen et al 2004, Huneau et al 2018, Moreton et al 2018].
Pathophysiology. Cerebral blood supply in individuals with CADASIL is reduced below demand, as demonstrated by an increased oxygen extraction rate in asymptomatic and demented individuals with CADASIL. Cerebral blood flow, cerebral blood volume, and cerebral glucose utilization are significantly reduced [Bruening et al 2001, Tuominen et al 2004]. In addition, cerebral vasoreactivity is impaired [Pfefferkorn et al 2001], consistent with the observed degeneration of vascular smooth muscle cells in small arteries and arterioles [Kalimo et al 2002]. Increased fragility of cerebral microvessels is suggested by a high frequency of cerebral microbleeds at autopsy and on gradient echo MRI [Lesnik Oberstein et al 2001, Dichgans et al 2002].
### Genotype-Phenotype Correlations
Smaller studies have described genotype-phenotype correlations for specific pathogenic variants [Lesnik Oberstein et al 2001, Arboleda-Velasquez et al 2002, Opherk et al 2004, Bianchi et al 2010]; however, none of these associations have been firmly established.
In general, affected individuals with cysteine-altering pathogenic variants in epidermal growth-factor like repeat (EGFr) domains 1-6 of NOTCH3 have a 12-year earlier onset of stroke, lower survival, and increased white matter hyperintensity volume, consistent with the more severe classic CADASIL presentation, compared to those with a cysteine-altering pathogenic variant in EGFr domains 7-34. The mean survival time was 68.5 and 76.9 years, respectively [Rutten et al 2019].
There is conflicting evidence about the effect of pathogenic variants in the ligand-binding domain of NOTCH3 (EGFr domains 10 and 11). Both a more severe and a milder phenotype have been described in small series [Arboleda-Velasquez et al 2002, Monet-Leprêtre et al 2009, Rutten et al 2019] (see also Penetrance).
Biallelic pathogenic variants in NOTCH3 have been described in individuals with CADASIL [Tuominen et al 2001, Liem et al 2008b, Ragno et al 2013, Soong et al 2013, Vinciguerra et al 2014, Abou Al-Shaar et al 2016]. The phenotype of individuals with biallelic NOTCH3 pathogenic variants falls within the CADASIL spectrum.
### Penetrance
Pathogenic variants in EGFr domains 1-6 appear to be fully penetrant and are usually associated with the classical CADASIL phenotype. However, there is variability in disease severity.
Pathogenic variants in EGFr domains 7-34 have a much higher population frequency (~1:300) [Rutten et al 2016a, Rutten et al 2019] and therefore likely predispose to a milder small-vessel disease and may even be non-penetrant.
### Nomenclature
Previous descriptions of families with "hereditary multi-infarct dementia," "chronic familial vascular encephalopathy," and "familial subcortical dementia" represent early reports of CADASIL.
### Prevalence
While most published information on individuals with CADASIL originates from Europe, CADASIL has been observed on all continents. Multiple small and national European registries have estimated the minimum prevalence at between two and four per 100,000 [Kalimo et al 2002, Razvi et al 2005b, Narayan et al 2012, Bianchi et al 2015].
Recently, it was found that the frequency of NOTCH3 cysteine-altering pathogenic variants is 1:300 in the general population worldwide (gnomAD), with the highest frequency in people who are from Asian descent (1:100) [Rutten et al 2016a, Rutten et al 2019]. This is approximately 100-fold higher than current estimates of the minimum prevalence of CADASIL, suggesting that CADASIL is much more prevalent than previously suspected and that the NOTCH3 clinical spectrum must be considerably broader, ranging from classic CADASIL to a much milder small-vessel disease, or possibly even non-penetrance.
## Differential Diagnosis
The differential diagnosis of CADASIL includes sporadic/multifactorial disorders and inherited disorders.
### Sporadic/Multifactorial Disorders
The clinical characteristics and MRI abnormalities in these conditions may resemble those of CADASIL. The presence of temporopolar MRI lesions, the absence of optic nerve and spinal cord involvement, the absence of oligoclonal bands in the cerebrospinal fluid, and the absence of hypertension are critical in this regard [Dichgans et al 1999] (see Table 2).
### Table 2.
Clinical Signs and MRI Abnormalities of Sporadic/Multifactorial Disorders in the Differential Diagnosis of CADASIL
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DisorderDistinguishing Clinical CharacteristicsDistinguishing MRI AbnormalitiesTemporopolar MRI LesionsOptic Nerve & Spinal Cord InvolvementOligoclonal Bands in CSFHypertension
Multiple sclerosis 1
* Optic neuritis
* Spinal cord involvement
* Internuclear ophthalmoplegia
* Lhermitte sign
* Heat sensitivity
* Age of onset: 15-50 yrs
* Juxtacortical WMH
* Dawson fingers
* Spinal cord, corpus callosum & U-fibers involvement
* Gadolinium enhancement of lesions
CommonTypicalYesNot associated
Sporadic small vessel disease incl Binswanger's disease
* Hypertension
* Absence of AD or AR inheritance in family history
* Age of onset: >65 yrs
* Involvement of temporal pole is rare
* Involvement of external capsule occurs less frequently
RareNoNoAssociated
Primary angiitis of the nervous system 2
* Subacute headache
* Multifocal neurologic deficits
* Signs & symptoms suggestive of systemic vaculitis (peripheral neuropathy, fever, weight loss, rash, & night sweats)
* May occur at any age; median age at diagnosis: 50 yrs
* Multifocal infarcts in different vascular territories
* Diffuse gadolinium enhanced lesions
UncommonInvolvement of:
* Spinal cord: 5% of affected individuals
* Optic nerve: rare
OccasionallyNot associated
AD = autosomal dominant; AR = autosomal recessive; CSF = cerebrospinal fluid; WMH = white matter hyperintensities
1\.
Joshi et al [2017]
2\.
Williamson et al [1999]
### Inherited Disorders
Several inherited disorders are associated with acute ischemic events (or stroke-like episodes in the case of MELAS) and cerebral white matter hyperintensities on MRI. These disorders can be distinguished from CADASIL by the associated clinical signs, MRI, mode of inheritance, and appropriate laboratory investigations (particularly, molecular genetic testing) (see Table 3).
### Table 3.
Clinical Signs and MRI Abnormalities of Inherited Disorders to Consider in the Differential Diagnosis of CADASIL
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DisorderGene(s)MOIDistinguishing Clinical SignsDistinguishing MRI Abnormalities
Fabry diseaseGLAXLClassic Fabry disease phenotype:
* Onset in childhood & adolescence
* Periodic severe pain in extremities
* Angiokeratoma
* Renal insufficiency
* Hypohidrosis
* Cardiac involvement
* Corneal opacities
Late-onset Fabry disease phenotype:
* Onset in adulthood & later
* Cardiomyopathy
* Renal disease
* Cerebrovascular disease
* Exclusive involvement of pulvinar thought to be characteristic
* Ischemic strokes predominantly located in vertebrobasilar system
* Vertebrobasilar dolichoectasia
CARASIL 1HTRA1AR
* Onset age: 20-30 yrs (spastic gait)
* Spastic gait
* Premature alopecia
* Severe low back pain & deforming spondylosis
* Spinal spondylosis
* In advanced stage: "arc" sign (involvement of pontocerebellar tract)
HTRA1 cerebral small vessel disease (CADASIL type 2)AD
* Onset age: 50-70 yrs (stroke)
* Alopecia, spondylosis, & low back pain reported (less frequently than in CARASIL)
Spinal spondylosis
MELAS 2MT-TL1
MT-ND5 3Mat
* Onset age: 2-10 yrs
* Anorexia
* Recurrent vomiting
* Short stature
* Generalized tonic-clonic seizures
* Proximal limb weakness
* Sensorineural hearing loss
* Stroke-like episodes of cortical blindness and/or altered consciousness from age ~40 yrs
* ↑ T2 signal, involving the posterior cerebrum, not conforming to the distribution of major arteries
* Swollen gyri
* Gadolinium enhancement of lesions
* Slow spreading of stroke-like lesions
CARASAL 4CTSAAD
* Age of onset: 40-60 yrs
* Intracerebral hemorrhage
* Muscle cramps
* Xerostomia
* Keratoconjuctivitis sicca
* Therapy-resistant hypertension
Intracerebral hemorrhages
COL4A1\- & COL4A2- related small vessel disease
(see COL4A1-Related Disorders & OMIM PS175780) 5COL4A1
COL4A2AD
* Highly variable clinical spectrum; onset range: infantile to (late) adult
* Infantile onset:
* Psychomotor retardation
* Infantile hemiplegia
* Intracerebral hemorrhage
* Seizures
* Adult onset:
* Intracerebral hemorrhage
* Opthalmologic abnormalities
* Renal abnormalities
* Cardiovascular abnormalties
* Muscle cramps
* Porencephaly
* Schizencephaly
* Deep & lobar intracerebral hemorrhage
* Cerebral calcification
* Cerebellar atrophy
* Intracranial aneurysms
AD = autosomal dominant; AR = autosomal recessive; Mat = maternal; MOI = mode of inheritance; WMH = white matter hyperintensities; XL = X-linked
1\.
CARASIL = cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
2\.
MELAS = mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
3\.
Pathogenic variants known to cause MELAS have been identified in other mtDNA tRNA genes including MT-TC, MT-TK, MT-TV, MT-TF, MT-TQ, MT-TS1, MT-TS2, and MT-TW, and in the protein-encoding genes MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND3, and MT-ND6.
4\.
CARASAL = cathepsin A–related arteriopathy with strokes and leukoencephalopathy [Bugiani et al 2016]
5\.
Meuwissen et al [2015]
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with CADASIL, the following evaluations are recommended, if they have not already been completed.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with CADASIL
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System/ConcernEvaluationComment
NeurologicComplete neurologic evaluation
Standard brain MRI incl FLAIR sequence & T2-weighted gradient echo imagingTo determine the extent of disease & to have a baseline measure for follow up
NeurodevelopmentalPsychometricsW/particular attention to executive function
Psychiatric/
BehavioralConsider referral to a psychiatrist.For treatment of mood disorders & evaluation of apathy
Miscellaneous/
OtherConsultation w/a clinical geneticist &/or genetic counselorTo include genetic counseling
Family support/resourcesAssess use of community or online resources.
Social work involvement for support
Home nursing referral, if needed
### Treatment of Manifestations
Discussion of medical management options for individuals with CADASIL have been published [del Río-Espínola et al 2009, Di Donato et al 2017].
### Table 5.
Treatment of Manifestations in Individuals with CADASIL
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Manifestation/
SituationTreatmentConsiderations/Other
Acute stroke/
TIAStandard supportive treatment following the guidelines of stroke medicineThe effect of thrombolytic therapy (intravenous thrombolysis) is unknown; there is no evidence or rationale for thrombolysis in those w/CADASIL, and the risk of intracerebral hemorrhage is probably increased; see Agents/Circumstances to Avoid.
MigraineSymptomatic treatment, which may include triptans & ergot derivativesThere is NO evidence that triptans or ergot derivatives are contraindicated due to their vasoconstrictive mechanism of action. 1
Psychiatric disturbanceStandard treatment 2Psychometric & psychiatric evaluation can be used to evaluate whether apathy (if present) is a symptom of depression or of cognitive dysfunction.
TIA = transient ischemic attack
1\.
Triptans appear to have the same treatment responses and frequency of serious side effects in individuals with CADASIL as in the general migraine population [Tan & Markus 2016].
2\.
No studies have been performed in individuals with CADASIL to determine the effect of the treatment of psychiatric disturbances (e.g. depression) with psychiatric drugs.
### Prevention of Primary Manifestations
No treatment is of proven efficacy in preventing stroke, vascular dementia, or CADASIL disease progression.
### Table 6.
Prevention of Primary Manifestations in Individuals with CADASIL
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Manifestation/
SituationPreventionConsiderations/Other
Stroke/TIAConsider antiplatelet therapy. 1The effect of antiplatelet therapy in individuals w/CADASIL is unknown and there is no evidence or rationale for its use in treatment of CADASIL – though also no evidence that it is contraindicated.
Control of vascular risk factorsIncl hypertension, diabetes, hypercholesterolemia, & smoking
MigraineConsider prophylactic therapy.Depending on migraine frequency
1\.
Such as aspirin and clopidogrel
### Surveillance
No standard international surveillance guidelines for CADASIL exist. Several countries have developed CADASIL guidelines, such as the medical guideline for CADASIL published (in French) by the French Health Authority (HAS).
The interval at which individuals with CADASIL should be seen for follow up depends on the severity and type of symptoms and the needs of patients and their care givers.
* Follow up by a neurologist with expertise in CADASIL is recommended from the time of diagnosis onward.
* A consultation with a neuropsychiatrist is recommended when there are symptoms of depression, apathy, or other psychiatric manifestations.
* Consultation of other medical specialists (e.g., rehabilitation physician, clinical geneticist, physical therapist, and psychologist) is as required.
### Agents/Circumstances to Avoid
The treatment effect of thrombolytic therapy (intravenous thrombolysis) is unknown in individuals with CADASIL. Studies performed in non-CADASIL populations show that increasing cerebral microbleed burden and increasing white matter hyperintensity lesion load is associated with an increased risk of intracerebral hemorrhage after thrombolytic therapy [Charidimou et al 2016, Charidimou et al 2017b]; therefore, individuals with CADASIL may be at increased risk for intracerebral hemorrhage. In case of a thromboembolic large vessel stroke (i.e., unrelated to CADASIL), the benefit of thrombolysis outweighs the potential risk of intracerebral hemorrhage.
Oral anticoagulants could lead to an increased risk of intracerebral hemorrhage in individuals with CADASIL due to the presence of microbleeds [Charidimou et al 2017a]; the prescription of anticoagulants should therefore be carefully weighed. In case of a clear indication for anticoagulant therapy, such as atrial fibrillation or deep venous thrombosis, the benefit of the treatment likely outweighs the potential risk of intracerebral hemorrhage.
Smoking increases the risk of stroke in individuals with CADASIL and should be avoided [Singhal et al 2004].
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Fetuses affected with CADASIL are not at an increased risk for intrauterine complications or complications during/after delivery [Donnini et al 2017].
In a retrospective study, women with CADASIL were at increased risk for neurologic events in pregnancy during and shortly after delivery (puerperium) [Roine et al 2005]. However, another retrospective study of 50 affected women and prospectively collected data of six women showed no association between CADASIL and risk for neurologic events or problems during pregnancy [Donnini et al 2017]. In the authorsʹ experience, most women with CADASIL have an uncomplicated pregnancy and delivery, but transient neurologic events are sometimes reported (mostly consistent with migraine aura) [Lesnik Oberstein, unpublished observation based on clinical practice].
### Therapies Under Investigation
Case reports and small-scale observational studies have suggested a beneficial effect of acetazolamide on migraine [Weller et al 1998, Forteza et al 2001, Donnini et al 2012]. Acetazolamide has also been shown to have a beneficial effect on cerebral perfusion [Chabriat et al 2000, Huang et al 2010, Park et al 2011, Fujiwara et al 2012]. Acetazolamide is not given to individuals with CADASIL on a routine basis, as no large studies have been performed.
Several therapeutic approaches are in pre-clinical development: testing in cells and mouse models including immunotherapy [Machuca-Parra et al 2017, Ghezali et al 2018], antisense mediated NOTCH3 exon skipping [Rutten et al 2016b], and treatment with stem cell factor and granulocyte colony-stimulating factor [Liu et al 2015].
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.
### Other
Cross-sectional and longitudinal studies suggest that disease progression is faster in individuals with CADASIL who have increased blood pressure [Peters et al 2004, Holtmannspötter et al 2005, Peters et al 2006, Ling et al 2017]. However, no controlled data regarding the effect of antihypertensive treatment on disease progression are available.
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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
| CADASIL | c0751587 | 2,386 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1500/ | 2021-01-18T21:38:49 | {"mesh": ["D046589"], "synonyms": ["Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy"]} |
Virus-associated trichodysplasia spinulosa is a rare infectious skin disease characterized by the development of follicular papules with keratin spicules in various parts of the body, predominantly in the face (e.g. nose, eyebrows, auricles), that is due to polyomavirus infection in immunocompromized patients.
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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
| Virus-associated trichodysplasia spinulosa | c3267126 | 2,387 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228379 | 2021-01-23T17:22:26 | {"umls": ["C3267126"], "synonyms": ["Cyclosporine-induced folliculodystrophy", "Pilomatrix dysplasia", "TS", "Trichodysplasia spinulosa", "VATS"]} |
A number sign (#) is used with this entry because of evidence that inflammatory bowel disease-25 (IBD25) is caused by homozygous mutation in the IL10RB gene (123889) on chromosome 21q22.
Another form of early-onset inflammatory bowel disease, IBD28 (613148), is caused by mutation in the IL10RA gene (146933) encoding the IL10R1 protein which, together with the IL10R2 protein encoded by IL10RB, forms the heterotetrameric IL10 (124092) receptor.
For a general description and discussion of genetic heterogeneity of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis, see IBD1 (266600).
Clinical Features
Glocker et al. (2009) reported a brother and sister from a consanguineous Turkish family, who presented in the first year of life with cutaneous folliculitis, proctitis, perianal abscesses, enterocutaneous fistulas, and, in the girl, rectovaginal fistula. Both sibs underwent multiple surgical interventions, including bowel resections, colostomy, and ileostomy. The sibs also had recurrent infections, believed to be related to immunosuppressive therapy, including otitis media, bronchitis, pneumonia, purulent gonarthritis, and renal abscess. The boy received an allogeneic hematopoietic stem cell transplant from an unaffected HLA-matched sib; shortly after transplantation, the cutaneous folliculitis and inflammatory anal fistulas resolved, and the patient remained in continuous remission from ileocolitis more than a year later.
Begue et al. (2011) studied a French boy who had onset of perianal lesions and pancolitis with granulomas at 3 months of age. He later developed epidodes of cutaneous folliculitis as well as bronchial infections, and also experienced 1 episode of mastoiditis. The patient's hematopoietic cells and intestinal tissue showed no response to IL10 or IL22 (605330), respectively.
Mapping
Kugathasan et al. (2008) carried out a genomewide association analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. They identified significant association between a SNP at chromosome 21q22, rs2836878 (P = 6.01 x 10(-8); odds ratio = 0.73) and pediatric-onset IBD. This SNP was replicated in an independent replication cohort and the Wellcome Trust Case Control Consortium (2007) CD cohort with similar odds ratios and a combined P value of 4.48 x 10(-12). The 21q22 signal resides in a small region of linkage disequilibrium (LD) that harbors no genes, but the nearest gene is PSMG1 (605296). Kugathasan et al. (2008) observed a modest increase in colonic expression of PSMG1 in IBD cases compared to controls. However, the expression did not vary with either the degree of mucosal inflammation or the carriage of the alleles at the 21q22 locus.
McGovern et al. (2010) combined new data from 2 genomewide association studies of ulcerative colitis involving 266,047 SNPs and performed a metaanalysis with previously published data (Silverberg et al., 2009), thus bringing together a discovery set of 2,693 European UC patients and 6,791 controls. McGovern et al. (2010) confirmed association with UC at rs2836878 (combined p = 1.4 x 10(-8)).
### Linkage with the IL10RB Gene
In a consanguineous Turkish family in which a brother and sister had early-onset severe enterocolitis, Glocker et al. (2009) performed genomewide microsatellite mapping and identified markers showing segregation with the phenotype on chromosome 21q; fine mapping narrowed the critical region to a 350-kb interval between D21S1257 and D21S1898.
Molecular Genetics
In a consanguineous Turkish family with early-onset severe enterocolitis, Glocker et al. (2009) sequenced the candidate gene IL10RB (123889) and identified homozygosity for a nonsense mutation in 2 affected sibs (123889.0002). The mutation was detected in heterozygosity in the unaffected parents and 2 unaffected sibs, but was not found in 180 German controls, 70 Turkish controls, or 30 Iranian controls. Glocker et al. (2009) analyzed the IL10RB gene in 90 patients with adult-onset IBD, 45 with Crohn disease and 45 with ulcerative colitis, but found no mutations or other sequence variations.
In a French boy with early-onset inflammatory bowel disease in whom hematopoietic cells showed a lack of response to IL10, Begue et al. (2011) identified homozygosity for a nonsense mutation in the IL10RB gene (123889.0003). His unaffected parents and brother were heterozygous for the mutation.
INHERITANCE \- Autosomal recessive ABDOMEN Gastrointestinal \- Severe enterocolitis in the first year of life \- Perianal abscess \- Proctitis \- Enterocutaneous fistula \- Rectovaginal fistula SKIN, NAILS, & HAIR Skin \- Cutaneous folliculitis \- Enterocutaneous fistula MISCELLANEOUS \- Onset of disease within the first year of life \- Patients may have recurrent infections due to immunosuppressive therapy MOLECULAR BASIS \- Caused by mutation in the gene encoding interleukin 10 receptor, beta (IL10RB, 123889.0002 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| INFLAMMATORY BOWEL DISEASE 25, AUTOSOMAL RECESSIVE | c2675508 | 2,388 | omim | https://www.omim.org/entry/612567 | 2019-09-22T16:01:12 | {"doid": ["0110909"], "mesh": ["C567251"], "omim": ["612567"], "orphanet": ["238569"], "synonyms": ["Alternative titles", "IL10-related early-onset inflammatory bowel disease", "IL10-related early-onset IBD", "INFLAMMATORY BOWEL DISEASE, EARLY-ONSET, AUTOSOMAL RECESSIVE"]} |
Erythrokeratoderma variabilis progressiva (EKVP) is a type of erythrokeratoderma characterized by the association of hyperkeratosis and erythema in persistent, although sometimes variable, circumscribed lesions. Progressive symmetric erythrokeratoderma (PSEK) and erythrokeratoderma variabilis (EKV) are probably no longer two distinctive diseases but rather the two clinical manifestations of a same disease, now known as EKVP.
## Epidemiology
Erythrokeratoderma is a rare skin disease whose prevalence has recently been estimated at around 1/ 2, 000,000 people. Both sexes are affected equally.
## Clinical description
The disease usually starts in the early months of life or later in infancy. Erythema at birth has been described. Patients present with well-demarcated, erythematous patches and hyperkeratotic plaques that are arranged symmetrically. The lesions favor the extensor surface of the upper and lower extremities, buttocks and face. The plaques tend to progress during childhood, with lesions stabilizing thereafter. Considerable clinical overlap exists between PSEK and EKV, the main distinguishing feature being the presence of migratory erythema in patients with EKV. The migratory aspects of the lesions may also change over time, according to lifetime periods. The palms and soles are usually normal but some patients may have palmoplantar keratoderma. Minimal pruritus may be noted. Improvement has rarely been reported.
## Etiology
EKVP is caused by mutations in the connexin genes GJB4 (1p35-p34), coding for connexin-30.3 or GJB3 (1p34), coding for connexin-31. Connexins are proteins that form gap junctions that allow the transport and signaling between neighboring cells in the epidermis. Since other unrelated multiethnic patients were negative for connexin genes, new causal genes are yet to be discovered. De novo mutations in GJA1 (6q22.31) were also reporting as causing EKVP.
## Diagnostic methods
Diagnosis is based on the presence of characteristic clinical features. The histopathological features are non-specific. Light microscopy, in the case of EKV, reveals orthokeratotic basket-weave hyperkeratosis, moderate to severe acanthosis with prominent granular layer, and papillomatosis; and in the case of PSEK, there is acanthosis of the epidermis with basket-weave and often patchy parakeratotic hyperkeratosis. The granular layer is prominent and sometimes shows intracellular vacuolization. Follicular plugging is not uncommon. Electron microscopy reveals, in the case of EKV, a reduced number of keratinosomes within the stratum granulosum and sometimes clumped tonofilaments; and in the case of PSEK, perinuclear vacuolization and lipid-like vacuoles or laminated inclusions in the stratum corneum, but these features are not diagnostic.
## Differential diagnosis
Differential diagnosis includes other diseases with erythematous and hyperkeratotic lesions such as KID syndrome, keratoderma hereditarium mutilans with ichthyosis, pityriasis rubra pilaris and psoriasis.
## Genetic counseling
The majority of cases follow an autosomal dominant mode of inheritance but approximately 40% occur sporadically. Autosomal recessive inheritance has also been described and should be considered when providing genetic counseling, especially in consanguineous families.
## Management and treatment
Treatment is symptomatic. Emollients are often used but their efficacy is limited. Topical keratolytics or oral acitretin can reduce the thickness of the lesions. Isotretinoin has been used instead of acitretin in some cases.
## Prognosis
EKVP is not a life threatening disease, but it may have an impact on the patient's quality of life and cause social handicap due to the skin's appearance. General health is unaffected.
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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
| Erythrokeratoderma variabilis progressiva | None | 2,389 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=308166 | 2021-01-23T18:37:44 | {"gard": ["10923"], "icd-10": ["Q82.8"]} |
Odynophagia
Pronunciation
* /oʊˌdɪnəˈfeɪdʒ(i)ə/
SpecialtyGastroenterology
Odynophagia is pain when swallowing.[1][2] The pain may be felt in the mouth or throat and can occur with or without difficulty swallowing.[3] The pain may be described as an ache, burning sensation, or occasionally a stabbing pain that radiates to the back.[4] Odynophagia often results in inadvertent weight loss. The term is from odyno- 'pain' and phagō 'to eat'.
## Contents
* 1 Causes
* 2 See also
* 3 References
* 4 External links
## Causes[edit]
Odynophagia may have environmental or behavioral causes, such as:
* Very hot or cold food and drinks (termed cryodynophagia when associated with cold drinks, classically in the setting of cryoglobulinaemia).
* Taking certain medications
* Using drugs, tobacco, or alcohol[3]
* Trauma or injury to the mouth, throat, or tongue[5]
It can also be caused by certain medical conditions, such as:
* Ulcers
* Abscesses
* Upper respiratory tract infections
* Inflammation or infection of the mouth, tongue, or throat (esophagitis, pharyngitis, tonsillitis, epiglottitis)[6]
* Immune disorders
* Oral or throat cancer[7]
## See also[edit]
* Phagophobia
## References[edit]
1. ^ "odynophagia". The American Heritage Science Dictionary. Houghton Mifflin Company. Retrieved 28 February 2017.
2. ^ "Medical Definition of Odynophagia". MedicineNet. 13 May 2016. Retrieved 28 February 2017.
3. ^ a b Schiff, Bradley A. (January 2016). "Ear, Nose, and Throat Disorders: Oropharyngeal Squamous Cell Carcinoma". Merck Manuals Professional Edition. Merck Sharp & Dohme Corp. Retrieved 28 February 2017.
4. ^ Allan B. Wolfson, ed. (2005). Harwood-Nuss' Clinical Practice of Emergency Medicine (4th ed.). pp. 307–8. ISBN 0-7817-5125-X.
5. ^ Scully, Crispian (2008). "Chapter 14: Soreness and ulcers". Oral and Maxillofacial Medicine: The Basis of Diagnosis and Treatment (2nd ed.). Edinburgh: Churchill Livingstone. pp. 131–139. ISBN 978-0-443-06818-8.
6. ^ Mayo Clinic Staff (8 August 2016). "Epiglottitis Symptoms". Mayo Clinic. Mayo Foundation for Medical Education and Research (MFMER). Retrieved 28 February 2017.
7. ^ "Search results for: Odynophagia". Merck Manuals Professional Edition. Merck Sharp & Dohme Corp. Retrieved 28 February 2017.
## External links[edit]
Quotations related to Odynophagia at Wikiquote
Classification
D
* ICD-10: R13
* ICD-9-CM: 787.20
* DiseasesDB: 17942
* v
* t
* e
Symptoms and signs relating to the human digestive system or abdomen
Gastrointestinal
tract
* Nausea
* Vomiting
* Heartburn
* Aerophagia
* Pagophagia
* Dysphagia
* oropharyngeal
* esophageal
* Odynophagia
* Bad breath
* Xerostomia
* Hypersalivation
* Burping
* Wet burp
* Goodsall's rule
* Chilaiditi syndrome
* Dance's sign
* Aaron's sign
* Arapov's sign
* Markle sign
* McBurney's point
* Sherren's triangle
* Radiologic signs: Hampton's line
* Klemm's sign
Accessory
* liver: Councilman body
* Mallory body
* biliary: Boas' sign
* Courvoisier's law
* Charcot's cholangitis triad/Reynolds' pentad
* cholecystitis (Murphy's sign
* Lépine's sign
* Mirizzi's syndrome)
* Nardi test
Defecation
* Flatulence
* Fecal incontinence
* Encopresis
* Fecal occult blood
* Rectal tenesmus
* Constipation
* Obstructed defecation
* Diarrhea
* Rectal discharge
* Psoas sign
* Obturator sign
* Rovsing's sign
* Hamburger sign
* Heel tap sign
* Aure-Rozanova's sign
* Dunphy sign
* Alder's sign
* Lockwood's sign
* Rosenstein's sign
Abdomen
Pain
* Abdominal pain
* Acute abdomen
* Colic
* Baby colic
* Abdominal guarding
* Blumberg sign
Distension
* Abdominal distension
* Bloating
* Ascites
* Tympanites
* Shifting dullness
* Ascites
* Fluid wave test
Masses
* Abdominal mass
* Hepatosplenomegaly
* Hepatomegaly
* Splenomegaly
Other
* Jaundice
* Mallet-Guy sign
* Puddle sign
* Ballance's sign
* Aortic insufficiency
* Castell's sign
* Kehr's sign
* Cullen's sign
* Grey Turner's sign
Hernia
* Howship–Romberg sign
* Hannington-Kiff sign
Other
* Cupola sign
* Fothergill's sign
* Carnett's sign
* Sister Mary Joseph nodule
This medical symptom 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
| Odynophagia | c0221150 | 2,390 | wikipedia | https://en.wikipedia.org/wiki/Odynophagia | 2021-01-18T18:56:36 | {"icd-9": ["787.20"], "icd-10": ["R13"], "wikidata": ["Q2455868"]} |
Autoimmune endocrine disease
Graves' disease
Other namesToxic diffuse goiter,
Flajani–Basedow–Graves disease
The classic finding of exophthalmos and lid retraction in Graves' disease
SpecialtyEndocrinology
SymptomsEnlarged thyroid, irritability, muscle weakness, sleeping problems, fast heartbeat, weight loss, poor tolerance of heat[1]
ComplicationsGraves' ophthalmopathy[1]
CausesUnknown[2]
Risk factorsFamily history, other autoimmune diseases[1]
Diagnostic methodBlood tests, radioiodine uptake[1][3]
TreatmentRadioiodine therapy, medications, thyroid surgery[1]
Frequency0.5% (males), 3% (females)[4]
Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid.[1] It frequently results in and is the most common cause of hyperthyroidism.[4] It also often results in an enlarged thyroid.[1] Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss.[1] Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy.[1] About 25 to 80% of people with the condition develop eye problems.[1][3]
The exact cause is unclear; however, it is believed to involve a combination of genetic and environmental factors.[2] A person is more likely to be affected if they have a family member with the disease.[1] If one twin is affected, a 30% chance exists that the other twin will also have the disease.[5] The onset of disease may be triggered by physical or emotional stress, infection or giving birth.[3] Those with other autoimmune diseases such as type 1 diabetes and rheumatoid arthritis are more likely to be affected.[1] Smoking increases the risk of disease and may worsen eye problems.[1] The disorder results from an antibody, called thyroid-stimulating immunoglobulin (TSI), that has a similar effect to thyroid stimulating hormone (TSH).[1] These TSI antibodies cause the thyroid gland to produce excess thyroid hormones.[1] The diagnosis may be suspected based on symptoms and confirmed with blood tests and radioiodine uptake.[1][3] Typically, blood tests show a raised T3 and T4, low TSH, increased radioiodine uptake in all areas of the thyroid and TSI antibodies.[3]
The three treatment options are radioiodine therapy, medications and thyroid surgery.[1] Radioiodine therapy involves taking iodine-131 by mouth, which is then concentrated in the thyroid and destroys it over weeks to months.[1] The resulting hypothyroidism is treated with synthetic thyroid hormones.[1] Medications such as beta blockers may control some of the symptoms, and antithyroid medications such as methimazole may temporarily help people while other treatments are having effect.[1] Surgery to remove the thyroid is another option.[1] Eye problems may require additional treatments.[1]
Graves disease will develop in about 0.5% of males and 3% of females.[4] It occurs about 7.5 times more often in women than in men.[1] Often, it starts between the ages of 40 and 60 but can begin at any age.[5] It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).[1][3] The condition is named after Irish surgeon Robert Graves, who described it in 1835.[5] A number of prior descriptions also exist.[5]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 2.1 Genetics
* 2.2 Infectious trigger
* 3 Mechanism
* 3.1 Pathophysiology
* 4 Diagnosis
* 4.1 Eye disease
* 5 Management
* 5.1 Antithyroid drugs
* 5.2 Radioiodine
* 5.3 Surgery
* 5.4 Eyes
* 6 Prognosis
* 7 Epidemiology
* 8 History
* 9 Society and culture
* 9.1 Notable cases
* 9.2 Literature
* 10 Research
* 11 References
* 12 External links
## Signs and symptoms[edit]
Main article: Signs and symptoms of Graves' disease
Graves disease symptoms
The signs and symptoms of Graves' disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being Graves' ophthalmopathy, goiter, and pretibial myxedema (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly insomnia, hand tremor, hyperactivity, hair loss, excessive sweating, oligomenorrhea, itching, heat intolerance, weight loss despite increased appetite, diarrhea, frequent defecation, palpitations, periodic partial muscle weakness or paralysis in those especially of Asian descent,[6] and skin warmth and moistness.[7] Further signs that may be seen on physical examination are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, lid lag, excessive lacrimation due to Graves' ophthalmopathy, arrhythmias of the heart, such as sinus tachycardia, atrial fibrillation, and premature ventricular contractions, and hypertension.[7] People with hyperthyroidism may experience behavioral and personality changes, including psychosis, mania, anxiety, agitation, and depression.[8]
## Cause[edit]
The exact cause is unclear; however, it is believed to involve a combination of genetic and environmental factors.[2] While a theoretical mechanism occurs by which exposure to severe stressors and high levels of subsequent distress such as PTSD(Post traumatic stress disorder) could increase the risk of autoimmune disease and cause an aggravation of the autoimmune response that leads to Graves' disease, more robust clinical data are needed for a firm conclusion.[9]
### Genetics[edit]
A genetic predisposition for Graves' disease is seen, with some people more prone to develop TSH receptor activating antibodies due to a genetic cause. Human leukocyte antigen DR (especially DR3) appears to play a role.[10] To date, no clear genetic defect has been found to point to a single-gene cause.
Genes believed to be involved include those for thyroglobulin, thyrotropin receptor, protein tyrosine phosphatase nonreceptor type 22, and cytotoxic T-lymphocyte–associated antigen 4, among others.[11]
### Infectious trigger[edit]
Since Graves' disease is an autoimmune disease which appears suddenly, often later in life, a viral or bacterial infection may trigger antibodies which cross-react with the human TSH receptor, a phenomenon known as antigenic mimicry.[12]
The bacterium Yersinia enterocolitica bears structural similarity with the human thyrotropin receptor[10] and was hypothesized to contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals.[13] In the 1990s, it was suggested that Y. enterocolitica may be an associated condition with both diseases having a shared inherited susceptibility.[14] More recently, the role for Y. enterocolitica has been disputed.[15]
Epstein-Barr virus (EBV) is another potential trigger.[16]
## Mechanism[edit]
Thyroid-stimulating immunoglobulins recognize and bind to the thyrotropin receptor (TSH receptor) which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3). Thyroxine receptors in the pituitary gland are activated by the surplus hormone, suppressing additional release of TSH in a negative feedback loop. The result is very high levels of circulating thyroid hormones and a low TSH level.
### Pathophysiology[edit]
Histopathological image of diffuse hyperplasia of the thyroid gland (clinically presenting as hyperthyroidism)
Graves' disease is an autoimmune disorder, in which the body produces antibodies to the receptor for thyroid-stimulating hormone. (Antibodies to thyroglobulin and to the thyroid hormones T3 and T4 may also be produced.)
These antibodies cause hyperthyroidism because they bind to the TSHr and chronically stimulate it. The TSHr is expressed on the thyroid follicular cells of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4. This, in turn, causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.
The infiltrative exophthalmos frequently encountered has been explained by postulating that the thyroid gland and the extraocular muscles share a common antigen which is recognized by the antibodies. Antibodies binding to the extraocular muscles would cause swelling behind the eyeball.
The "orange peel" skin has been explained by the infiltration of antibodies under the skin, causing an inflammatory reaction and subsequent fibrous plaques.
The three types of autoantibodies to the TSH receptor currently recognized are:
* Thyroid stimulating immunoglobulins: these antibodies (mainly IgG) act as long-acting thyroid stimulants, activating the cells in a longer and slower way than TSH, leading to an elevated production of thyroid hormone.
* Thyroid growth immunoglobulins: these antibodies bind directly to the TSH receptor and have been implicated in the growth of thyroid follicles.
* Thyrotrophin binding-inhibiting immunoglobulins: these antibodies inhibit the normal union of TSH with its receptor. Some actually act as if TSH itself is binding to its receptor, thus inducing thyroid function. Other types may not stimulate the thyroid gland, but prevent TSI and TSH from binding to and stimulating the receptor.
Another effect of hyperthyroidism is bone loss from osteoporosis, caused by an increased excretion of calcium and phosphorus in the urine and stool. The effects can be minimized if the hyperthyroidism is treated early. Thyrotoxicosis can also augment calcium levels in the blood by as much as 25%. This can cause stomach upset, excessive urination, and impaired kidney function.[17]
## Diagnosis[edit]
Graves' disease may present clinically with one or more of these characteristic signs:
* Rapid heartbeat (80%)
* Diffuse palpable goiter with audible bruit (70%)
* Tremor (40%)
* Exophthalmos (protuberance of one or both eyes), periorbital edema (25%)
* Fatigue (70%), weight loss (60%) with increased appetite in young people and poor appetite in the elderly, and other symptoms of hyperthyroidism/thyrotoxicosis
* Heat intolerance (55%)
* Tremulousness (55%)
* Palpitations (50%)
Two signs are truly 'diagnostic' of Graves' disease (i.e., not seen in other hyperthyroid conditions): exophthalmos and nonpitting edema (pretibial myxedema). Goiter is an enlarged thyroid gland and is of the diffuse type (i.e., spread throughout the gland). Diffuse goiter may be seen with other causes of hyperthyroidism, although Graves' disease is the most common cause of diffuse goiter. A large goiter will be visible to the naked eye, but a small one (mild enlargement of the gland) may be detectable only by physical examination. Occasionally, goiter is not clinically detectable, but may be seen only with computed tomography or ultrasound examination of the thyroid.
Another sign of Graves' disease is hyperthyroidism, i.e., overproduction of the thyroid hormones T3 and T4. Normal thyroid levels are also seen, and occasionally also hypothyroidism, which may assist in causing goiter (though it is not the cause of the Graves' disease). Hyperthyroidism in Graves' disease is confirmed, as with any other cause of hyperthyroidism, by measuring elevated blood levels of free (unbound) T3 and T4.
Other useful laboratory measurements in Graves' disease include thyroid-stimulating hormone (TSH, usually undetectable in Graves' disease due to negative feedback from the elevated T3 and T4), and protein-bound iodine (elevated). Serologically detected thyroid-stimulating antibodies, radioactive iodine (RAI) uptake, or thyroid ultrasound with Doppler all can independently confirm a diagnosis of Graves' disease.
Biopsy to obtain histiological testing is not normally required, but may be obtained if thyroidectomy is performed.
The goiter in Graves' disease is often not nodular, but thyroid nodules are also common.[18] Differentiating common forms of hyperthyroidism such as Graves' disease, single thyroid adenoma, and toxic multinodular goiter is important to determine proper treatment.[18] The differentiation among these entities has advanced, as imaging and biochemical tests have improved. Measuring TSH-receptor antibodies with the h-TBII assay has been proven efficient and was the most practical approach found in one study.[19]
### Eye disease[edit]
Further information: Graves' ophthalmopathy
Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease (TED), is the most common extrathyroidal manifestation of Graves' disease. It is a form of idiopathic lymphocytic orbital inflammation, and although its pathogenesis is not completely understood, autoimmune activation of orbital fibroblasts, which in TAO express the TSH receptor, is thought to play a central role.[20]
Hypertrophy of the extraocular muscles, adipogenesis, and deposition of nonsulfated glycoaminoglycans and hyaluronate, causes expansion of the orbital fat and muscle compartments, which within the confines of the bony orbit may lead to dysthyroid optic neuropathy, increased intraocular pressures, proptosis, venous congestion leading to chemosis and periorbital edema, and progressive remodeling of the orbital walls.[21][22][23] Other distinctive features of TAO include lid retraction, restrictive myopathy, superior limbic keratoconjunctivitis, and exposure keratopathy.
Severity of eye disease may be classified by the mnemonic: "NO SPECS":[24]
* Class 0: No signs or symptoms
* Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)
* Class 2: Soft tissue involvement (oedema of conjunctivae and lids, conjunctival injection, etc.)
* Class 3: Proptosis
* Class 4: Extraocular muscle involvement (usually with diplopia)
* Class 5: Corneal involvement (primarily due to lagophthalmos)
* Class 6: Sight loss (due to optic nerve involvement)
Typically the natural history of TAO follows Rundle's curve, which describes a rapid worsening during an initial phase, up to a peak of maximum severity, and then improvement to a static plateau without, however, resolving back to a normal condition.[25]
## Management[edit]
Treatment of Graves' disease includes antithyroid drugs which reduce the production of thyroid hormone; radioiodine (radioactive iodine I-131); and thyroidectomy (surgical excision of the gland). As operating on a frankly hyperthyroid patient is dangerous, prior to thyroidectomy, preoperative treatment with antithyroid drugs is given to render the patient "euthyroid" (i.e. normothyroid). Each of these treatments has advantages and disadvantages. No one treatment approach is considered the best for everyone.
Treatment with antithyroid medications must be given for six months to two years to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. The risk of recurrence is about 40–50%, and lifelong treatment with antithyroid drugs carries some side effects such as agranulocytosis and liver disease.[26] Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells. Therapy with radioiodine is the most common treatment in the United States, while antithyroid drugs and/or thyroidectomy are used more often in Europe, Japan, and most of the rest of the world.
β-Blockers (such as propranolol) may be used to inhibit the sympathetic nervous system symptoms of tachycardia and nausea until such time as antithyroid treatments start to take effect. Pure β-blockers do not inhibit lid-retraction in the eyes, which is mediated by alpha adrenergic receptors.
### Antithyroid drugs[edit]
The main antithyroid drugs are carbimazole (in the UK), methimazole (in the US), and propylthiouracil/PTU. These drugs block the binding of iodine and coupling of iodotyrosines. The most dangerous side effect is agranulocytosis (1/250, more in PTU). Others include granulocytopenia (dose-dependent, which improves on cessation of the drug) and aplastic anemia. Patients on these medications should see a doctor if they develop sore throat or fever. The most common side effects are rash and peripheral neuritis. These drugs also cross the placenta and are secreted in breast milk. Lugol's iodine may be used to block hormone synthesis before surgery.
A randomized control trial testing single-dose treatment for Graves' found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).[27]
No difference in outcome was shown for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are a positive TSHr antibody (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (sensitivity 39%, specificity 98%), a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.[28]
### Radioiodine[edit]
Scan of affected thyroid before (top) and after (bottom) radioiodine therapy
Radioiodine (radioactive iodine-131) was developed in the early 1940s at the Mallinckrodt General Clinical Research Center. This modality is suitable for most patients, although some prefer to use it mainly for older patients. Indications for radioiodine are failed medical therapy or surgery and where medical or surgical therapy are contraindicated. Hypothyroidism may be a complication of this therapy, but may be treated with thyroid hormones if it appears. The rationale for radioactive iodine is that it accumulates in the thyroid and irradiates the gland with its beta and gamma radiations, about 90% of the total radiation being emitted by the beta (electron) particles. The most common method of iodine-131 treatment is to administer a specified amount in microcuries per gram of thyroid gland based on palpation or radiodiagnostic imaging of the gland over 24 hours.[29] Patients who receive the therapy must be monitored regularly with thyroid blood tests to ensure they are treated with thyroid hormone before they become symptomatically hypothyroid.[30]
Contraindications to RAI are pregnancy (absolute), ophthalmopathy (relative; it can aggravate thyroid eye disease), or solitary nodules.[31]
Disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring eventual thyroid hormone supplementation in the form of a daily pill(s). The radioiodine treatment acts slowly (over months to years) to destroy the thyroid gland, and Graves' disease-associated hyperthyroidism is not cured in all persons by radioiodine, but has a relapse rate that depends on the dose of radioiodine which is administered.[31] In rare cases, radiation induced thyroiditis has been linked to this treatment.[32]
### Surgery[edit]
Further information: Thyroidectomy
This modality is suitable for young and pregnant people. Indications for thyroidectomy can be separated into absolute indications or relative indications. These indications aid in deciding which people would benefit most from surgery.[26] The absolute indications are a large goiter (especially when compressing the trachea), suspicious nodules or suspected cancer (to pathologically examine the thyroid), and people with ophthalmopathy and additionally if it is the person's preferred method of treatment or if refusing to undergo radioactive iodine treatment. Pregnancy is advised to be delayed for 6 months after radioactive iodine treatment.[26]
Both bilateral subtotal thyroidectomy and the Hartley-Dunhill procedure (hemithyroidectomy on one side and partial lobectomy on other side) are possible.
Advantages are immediate cure and potential removal of carcinoma. Its risks are injury of the recurrent laryngeal nerve, hypoparathyroidism (due to removal of the parathyroid glands), hematoma (which can be life-threatening if it compresses the trachea), relapse following medical treatment, infections (less common), and scarring.[26] The increase in the risk of nerve injury can be due to the increased vascularity of the thyroid parenchyma and the development of links between the thyroid capsule and the surrounding tissues. Reportedly, a 1% incidence exists of permanent recurrent laryngeal nerve paralysis after complete thyroidectomy.[26] Removal of the gland enables complete biopsy to be performed to have definite evidence of cancer anywhere in the thyroid. (Needle biopsies are not so accurate at predicting a benign state of the thyroid). No further treatment of the thyroid is required, unless cancer is detected. Radioiodine uptake study may be done after surgery, to ensure all remaining (potentially cancerous) thyroid cells (i.e., near the nerves to the vocal cords) are destroyed. Besides this, the only remaining treatment will be levothyroxine, or thyroid replacement pills to be taken for the rest of the patient's life.
A 2013 review article concludes that surgery appears to be the most successful in the management of Graves' disease, with total thyroidectomy being the preferred surgical option.[33]
### Eyes[edit]
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Mild cases are treated with lubricant eye drops or nonsteroidal anti-inflammatory drops. Severe cases threatening vision (corneal exposure or optic nerve compression) are treated with steroids or orbital decompression. In all cases, cessation of smoking is essential. Double vision can be corrected with prism glasses and surgery (the latter only when the process has been stable for a while).
Difficulty closing eyes can be treated with lubricant gel at night, or with tape on the eyes to enable full, deep sleep.
Orbital decompression can be performed to enable bulging eyes to retreat back into the head. Bone is removed from the skull behind the eyes, and space is made for the muscles and fatty tissue to fall back into the skull.
Eyelid surgery can be performed on upper and/or lower eyelids to reverse the effects of Graves' disease[34] on the eyelids. Eyelid muscles can become tight with Graves' disease, making it impossible to close eyes all the way. Eyelid surgery involves an incision along the natural crease of the eyelid, and a scraping away of the muscle that holds the eyelid open. This makes the muscle weaker, which allows the eyelid to extend over the eyeball more effectively. Eyelid surgery helps reduce or eliminate dry eye symptoms.
For management of clinically active Graves' disease, orbitopathy (clinical activity score >2) with at least mild to moderate severity, intravenous glucocorticoids are the treatment of choice, usually administered in the form of pulse intravenous methylprednisolone. Studies have consistently shown that pulse intravenous methylprednisolone is superior to oral glucocorticoids both in terms of efficacy and decreased side effects for managing Graves' orbitopathy.[35]
## Prognosis[edit]
If left untreated, more serious complications could result, including birth defects in pregnancy, increased risk of a miscarriage, bone mineral loss[36] and, in extreme cases, death. Graves' disease is often accompanied by an increase in heart rate, which may lead to further heart complications, including loss of the normal heart rhythm (atrial fibrillation), which may lead to stroke. If the eyes are proptotic (bulging) enough that the lids do not close completely at night, dryness will occur – with the risk of a secondary corneal infection, which could lead to blindness. Pressure on the optic nerve behind the globe can lead to visual field defects and vision loss, as well. Prolonged untreated hyperthyroidism can lead to bone loss, which may resolve when treated.[36]
## Epidemiology[edit]
Graves' disease occurs in about 0.5% of people.[3] Graves' disease data has shown that the lifetime risk for women is around 3% and 0.5% for men. [37]It occurs about 7.5 times more often in women than in men.[1] Often it starts between the ages of 40 and 60.[5] It is the most common cause of hyperthyroidism in the United States (about 50 to 80% of cases).[1][3]
## History[edit]
Graves' disease owes its name to the Irish doctor Robert James Graves,[38] who described a case of goiter with exophthalmos in 1835.[39] Medical eponyms are often styled nonpossessively; thus Graves' disease and Graves disease are variant stylings of the same term.
The German Karl Adolph von Basedow independently reported the same constellation of symptoms in 1840.[40][41] As a result, on the European Continent, the terms Basedow's syndrome,[42] Basedow's disease, or Morbus Basedow[43] are more common than Graves' disease.[42][44]
Graves' disease[42][43] has also been called exophthalmic goiter.[43]
Less commonly, it has been known as Parry's disease,[42][43] Begbie's disease, Flajani's disease, Flajani–Basedow syndrome, and Marsh's disease.[42] These names for the disease were derived from Caleb Hillier Parry, James Begbie, Giuseppe Flajani, and Henry Marsh.[42] Early reports, not widely circulated, of cases of goiter with exophthalmos were published by the Italians Giuseppe Flajani[45] and Antonio Giuseppe Testa,[46] in 1802 and 1810, respectively.[47] Prior to these, Caleb Hillier Parry,[48] a notable provincial physician in England of the late 18th century (and a friend of Edward Miller-Gallus),[49] described a case in 1786. This case was not published until 1825, which was still ten years ahead of Graves.[50]
However, fair credit for the first description of Graves' disease goes to the 12th century Persian physician Sayyid Ismail al-Jurjani,[51] who noted the association of goiter and exophthalmos in his Thesaurus of the Shah of Khwarazm, the major medical dictionary of its time.[42][52][53]
## Society and culture[edit]
### Notable cases[edit]
Marty Feldman used his bulging eyes, caused by Graves' disease, for comedic effect.
Umm Kulthum in Life Magazine, 1962
* Ayaka, Japanese singer, was diagnosed with Graves' disease in 2007. After going public with her diagnosis in 2009, she took a two-year hiatus from music to focus on treatment.[54][55]
* Susan Elizabeth Blow, American educator and founder of the first publicly funded Kindergarten in the United States, was forced to retire and seek treatment for Graves Disease in 1884.[56]
* George H. W. Bush, former U.S. president, developed new atrial fibrillation and was diagnosed in 1991 with hyperthyroidism due to the disease and treated with radioactive iodine. The president's wife, Barbara Bush, also developed the disease around the same time, which, in her case, produced severe infiltrative exophthalmos.[57]
* Rodney Dangerfield, American comedian and actor[58]
* Gail Devers, American sprinter: A doctor considered amputating her feet after she developed blistering and swelling following radiation treatment for Graves' disease, but she went on to recover and win Olympic medals.
* Missy Elliott, American hip-hop artist[59]
* Marty Feldman, British comedy writer, comedian and actor[60][61]
* Sia Furler, Australian singer and songwriter[62]
* Sammy Gravano, Italian-American former underboss of the Gambino crime family.[63]
* Jim Hamilton, Scottish rugby player, discovered he had Graves' disease shortly after retiring from the sport in 2017.[64]
* Heino, German folk singer, whose dark sunglasses (worn to hide his symptoms) became part of his trademark look[65]
* Herbert Howells, British composer; the first person to be treated with radium injections[66]
* Yayoi Kusama, Japanese artist.[67]
* Nadezhda Krupskaya, Russian Communist and wife of Vladimir Lenin[68]
* Barbara Leigh, an American former actress and fashion model, now spokeswoman for the National Graves' Disease Foundation[69]
* Keiko Masuda, Japanese singer and one-half of the duo Pink Lady.[70][71][72][73]
* Yūko Miyamura, Japanese voice actress[74]
* Lord Monckton, former UKIP and Conservative politician and noted climate change skeptic.[75]
* Sophia Parnok, Russian poet[76][77][78]
* Sir Cecil Spring Rice, British ambassador to the United States during World War I, died suddenly of the disease in 1918.[79]
* Christina Rossetti, English Victorian-era poet[80]
* Dame Maggie Smith, British actress[81]
* Mary Webb, British novelist and poet[82]
* Umm Kulthum was an Egyptian singer, songwriter, and film actress active from the 1920s to the 1970s. She was given the honorific title Kawkab al-Sharq. Umm Kulthum was known for her vocal ability and unique style.
* Wendy Williams, American TV show host[83]
### Literature[edit]
In Italo Svevo's novel Zeno's Conscience, character Ada develops the disease.[84][85]
## Research[edit]
Agents that act as antagonists at thyroid stimulating hormone receptors are currently under investigation as a possible treatment for Graves' disease.[86]
## References[edit]
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40. ^ Von Basedow, KA. Exophthalmus durch Hypertrophie des Zellgewebes in der Augenhöhle. [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1840, 6: 197–204; 220–228. Partial English translation in: Ralph Hermon Major (1884–1970): Classic Descriptions of Disease. Springfield, C. C. Thomas, 1932. 2nd edition, 1939; 3rd edition, 1945.
41. ^ Von Basedow, KA. Die Glotzaugen. [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1848: 769–777.
42. ^ a b c d e f g Basedow's syndrome or disease at Who Named It? – the history and naming of the disease
43. ^ a b c d Robinson, Victor, ed. (1939). "Exophthalmic goiter, Basedow's disease, Grave's disesase". The Modern Home Physician, A New Encyclopedia of Medical Knowledge. WM. H. Wise & Company (New York)., pages 82, 294, and 295.
44. ^ Goiter, Diffuse Toxic at eMedicine
45. ^ Flajani, G. Sopra un tumor freddo nell'anterior parte del collo broncocele. (Osservazione LXVII). In Collezione d'osservazioni e reflessioni di chirurgia. Rome, Michele A Ripa Presso Lino Contedini, 1802;3:270–273.
46. ^ Testa, AG. Delle malattie del cuore, loro cagioni, specie, segni e cura. Bologna, 1810. 2nd edition in 3 volumes, Florence, 1823; Milano 1831; German translation, Halle, 1813.
47. ^ Giuseppe Flajani at Who Named It?
48. ^ Parry CH (1825). "Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart". Collections from the unpublished medical writings of C. H. Parry. London. pp. 111–129. "According to Garrison, Parry first noted the condition in 1786. He briefly reported it in his Elements of Pathology and Therapeutics, 1815. Reprinted in Medical Classics, 1940, 5: 8–30"
49. ^ Hull G (June 1998). "Caleb Hillier Parry 1755-1822: a notable provincial physician". Journal of the Royal Society of Medicine. 91 (6): 335–8. doi:10.1177/014107689809100618. PMC 1296785. PMID 9771526.
50. ^ Caleb Hillier Parry at Who Named It?
51. ^ Sayyid Ismail Al-Jurjani. Thesaurus of the Shah of Khwarazm.
52. ^ Ljunggren JG (August 1983). "[Who was the man behind the syndrome: Ismail al-Jurjani, Testa, Flagani, Parry, Graves or Basedow? Use the term hyperthyreosis instead]". Lakartidningen. 80 (32–33): 2902. PMID 6355710.
53. ^ Nabipour I (2003). "Clinical Endocrinology in the Islamic Civilization in Iran". International Journal of Endocrinology and Metabolism. 1: 43–45 [45].
54. ^ "水嶋ヒロ・絢香、2ショット会見で結婚報告 絢香はバセドウ病を告白、年内で休業へ" (in Japanese). Oricon. April 3, 2009. Archived from the original on December 8, 2015. Retrieved November 19, 2015.
55. ^ "絢香、初のセルフ・プロデュース・アルバムが発売決定！" (in Japanese). CDJournal. December 1, 2011. Archived from the original on October 15, 2015. Retrieved November 19, 2015.
56. ^ Shepley, Carol Ferring (2008). Movers and Shakers, Scalawags and Suffragettes: Tales from Bellefontaine Cemetery. St. Louis, Missouri: Missouri History Museum.
57. ^ Altman LK (1991-05-28). "The Doctor's World — A White House Puzzle: Immunity Ailments-Science Section". Nytimes.com. Archived from the original on 2013-05-08. Retrieved 2013-02-27.
58. ^ Islam S (2017-01-23). "Thyroid gland – Hyperplasia / goiter – Graves disease". Pathologyoutlines.com. Archived from the original on 2016-12-14. Retrieved 2017-01-25.
59. ^ Oldenburg A (2011-06-24). "Update: Missy Elliott 'completely managing' Graves' disease". USA Today. Gannett.
60. ^ "Famous People with Graves' Disease". HRFnd. December 15, 2013. Retrieved 2018-02-22.
61. ^ Kuhlenbeck M (June 29, 2016). "Marty Feldman versus the Suits". Jewish Currents. Retrieved 2018-02-22. "Viewers also could not help being amazed by his bulging eyes, which had resulted from a botched operation for Graves’ disease."
62. ^ Rota G. "Facts About Sia Furler | Popsugar Celebrity Australia". Popsugar.com.au. Archived from the original on 2015-02-09. Retrieved 2016-09-10.
63. ^ Guart, Al (March 31, 2002). "Rare Disease Could Whack Sammy Bull". New York Post. Retrieved January 28, 2020.
64. ^ "Hamilton talks about his disease on his podcast". Archived from the original on 2017-09-08.
65. ^ "Crossover Crooner: The Strange Comeback of Germany's Wannabe Johnny Cash". Spiegel.de. 2013-02-07. Archived from the original on 2014-11-19. Retrieved 2014-07-27.
66. ^ Spicer P (1998). Herbert Howells. Bridgend: Seren. p. 44. ISBN 1-85411-233-3.
67. ^ "Yayoi Kusama by Grady T. Turner". Bomb Magazine. January 1, 1999. Retrieved May 29, 2020.
68. ^ "Revolutionary First Lady: the life and struggles of Lenin's wife". Russia Beyond. Archived from the original on 2018-04-18. Retrieved 2018-04-18.
69. ^ "Barbara Leigh". Home.rmci.net. Archived from the original on 2012-07-10. Retrieved 2013-02-27.
70. ^ "［歌手 増田恵子さん］バセドー病（１）マイク持つ手が震える". Yomiuri Shimbun. 2011-08-04. Retrieved 2020-02-01.
71. ^ "［歌手 増田恵子さん］バセドー病（２）同じ病 姉の存在が支えに". Yomiuri Shimbun. 2011-08-11. Retrieved 2020-02-01.
72. ^ "［歌手 増田恵子さん］バセドー病（３）ツアー中、甲状腺腫れ上がる". Yomiuri Shimbun. 2011-08-18. Retrieved 2020-02-01.
73. ^ "［歌手 増田恵子さん］バセドー病（４）病気公表 無理せず我慢せず". Yomiuri Shimbun. 2011-08-25. Retrieved 2020-02-01.
74. ^ "親子知新". www3.bigcosmic.com. Archived from the original on May 15, 2007. Retrieved December 18, 2017.
75. ^ Rupert Murray "Meet the Climate Sceptics" Archived 2013-10-22 at the Wayback Machine, Storyville, 3 February 2011.
76. ^ "Sophia Parnok, Russia's Sappho".
77. ^ Burgin, Diana Lewis (1992). "Sophia Parnok and the Writing of a Lesbian Poet's Life". Slavic Review. 51 (2): 214–231. doi:10.2307/2499528. JSTOR 2499528.
78. ^ https://www.king.org/event/the-esoterics-parnok-in-that-infinite-moment/
79. ^ Simon, Bernard (31 May 2013). "This memorial is poetic justice for Sir Cecil Spring Rice". telegraph.co.uk. Archived from the original on 2014-03-12. Retrieved 2014-08-25.
80. ^ "Christina Rossetti". Poetry Foundation. Archived from the original on 2016-04-17. Retrieved 2016-09-10.
81. ^ Wolf M (March 18, 1990). "There is Nothing Like This Dame". New York Times. Archived from the original on August 10, 2016. Retrieved 2015-10-19.
82. ^ "Archived copy". Archived from the original on 2015-07-16. Retrieved 2015-07-16.CS1 maint: archived copy as title (link)
83. ^ Melas C (February 21, 2018). "Wendy Williams announces show hiatus due to Graves' disease". CNN. Retrieved February 21, 2018.
84. ^ Svevo, Italo (2003). Zeno's conscience : a novel (1st Vintage International ed.). Vintage Books. pp. 315–321. ISBN 0375727760.
85. ^ Scarponi, Mattia (19 August 2017). "Il morbo di Basedow: lo sfinimento tra Zeno e la realtà". theWise Magazine (in Italian). Retrieved 25 March 2020.
86. ^ "Thyroid". Mayo Clinic. Archived from the original on 4 November 2016. Retrieved 1 November 2016.
## External links[edit]
* "Graves' disease". Genetics Home Reference. U.S. National Library of Medicine.
Classification
D
* ICD-10: E05.0
* ICD-9-CM: 242.0
* OMIM: 275000
* MeSH: D006111
* DiseasesDB: 5419
* SNOMED CT: 353295004
External resources
* Curlie: Graves' disease
* MedlinePlus: 000358
* eMedicine: med/929 ped/899
* v
* t
* e
Thyroid disease
Hypothyroidism
* Iodine deficiency
* Cretinism
* Congenital hypothyroidism
* Myxedema
* Myxedema coma
* Euthyroid sick syndrome
* Signs and symptoms
* Queen Anne's sign
* Woltman sign
* Thyroid dyshormonogenesis
* Pickardt syndrome
Hyperthyroidism
* Hyperthyroxinemia
* Thyroid hormone resistance
* Familial dysalbuminemic hyperthyroxinemia
* Hashitoxicosis
* Thyrotoxicosis factitia
* Thyroid storm
Graves' disease
* Signs and symptoms
* Abadie's sign of exophthalmic goiter
* Boston's sign
* Dalrymple's sign
* Stellwag's sign
* lid lag
* Griffith's sign
* Möbius sign
* Pretibial myxedema
* Graves' ophthalmopathy
Thyroiditis
* Acute infectious
* Subacute
* De Quervain's
* Subacute lymphocytic
* Palpation
* Autoimmune/chronic
* Hashimoto's
* Postpartum
* Riedel's
Enlargement
* Goitre
* Endemic goitre
* Toxic nodular goitre
* Toxic multinodular goiter
* Thyroid nodule
* Colloid nodule
* v
* t
* e
Hypersensitivity and autoimmune diseases
Type I/allergy/atopy
(IgE)
Foreign
* Atopic eczema
* Allergic urticaria
* Allergic rhinitis (Hay fever)
* Allergic asthma
* Anaphylaxis
* Food allergy
* common allergies include: Milk
* Egg
* Peanut
* Tree nut
* Seafood
* Soy
* Wheat
* Penicillin allergy
Autoimmune
* Eosinophilic esophagitis
Type II/ADCC
* * IgM
* IgG
Foreign
* Hemolytic disease of the newborn
Autoimmune
Cytotoxic
* Autoimmune hemolytic anemia
* Immune thrombocytopenic purpura
* Bullous pemphigoid
* Pemphigus vulgaris
* Rheumatic fever
* Goodpasture syndrome
* Guillain–Barré syndrome
"Type V"/receptor
* Graves' disease
* Myasthenia gravis
* Pernicious anemia
Type III
(Immune complex)
Foreign
* Henoch–Schönlein purpura
* Hypersensitivity vasculitis
* Reactive arthritis
* Farmer's lung
* Post-streptococcal glomerulonephritis
* Serum sickness
* Arthus reaction
Autoimmune
* Systemic lupus erythematosus
* Subacute bacterial endocarditis
* Rheumatoid arthritis
Type IV/cell-mediated
(T cells)
Foreign
* Allergic contact dermatitis
* Mantoux test
Autoimmune
* Diabetes mellitus type 1
* Hashimoto's thyroiditis
* Multiple sclerosis
* Coeliac disease
* Giant-cell arteritis
* Postorgasmic illness syndrome
* Reactive arthritis
GVHD
* Transfusion-associated graft versus host disease
Unknown/
multiple
Foreign
* Hypersensitivity pneumonitis
* Allergic bronchopulmonary aspergillosis
* Transplant rejection
* Latex allergy (I+IV)
Autoimmune
* Sjögren syndrome
* Autoimmune hepatitis
* Autoimmune polyendocrine syndrome
* APS1
* APS2
* Autoimmune adrenalitis
* Systemic autoimmune disease
Authority control
* BNE: XX531538
* BNF: cb121242921 (data)
* GND: 4144092-4
* LCCN: sh85056549
* NDL: 00560542
* NSK: 000092830
* SUDOC: 029667402
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Graves' disease | c0154138 | 2,391 | wikipedia | https://en.wikipedia.org/wiki/Graves%27_disease | 2021-01-18T18:59:04 | {"gard": ["6549"], "umls": ["C0154138"], "wikidata": ["Q16483"]} |
In a brother and sister born to nonconsanguineous parents, Davee et al. (1992) described renal hypoplasia, mullerian duct hypoplasia, and strikingly similar facial features. Facies consisted of frontal bossing, hypertelorism, strabismus, short nose, and mild micrognathia. Both sibs had severe growth and developmental retardation. A small horseshoe kidney and an absent uterus were the primary urogenital features in the girl. Her brother had an anteriorly displaced urethral meatus and a small right hydrocele; the left testis was in the inguinal canal and his kidneys were hypoplastic but functional.
HEENT \- Frontal bossing \- Hypertelorism \- Strabismus \- Short nose \- Mild micrognathia GU \- Renal hypoplasia \- Horseshoe kidney \- Absent uterus \- Anteriorly displaced urethral meatus \- Hydrocele \- Inguinal testis \- Mullerian duct hypoplasia Growth \- Severe growth retardation Neuro \- Severe developmental retardation Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| RENAL AND MULLERIAN DUCT HYPOPLASIA | c1849439 | 2,392 | omim | https://www.omim.org/entry/266810 | 2019-09-22T16:22:47 | {"mesh": ["C564853"], "omim": ["266810"]} |
Spinal muscular atrophy with respiratory distress type 2 is a rare, genetic, motor neuron disease characterized by progressive early respiratory failure associated with diaphragm paralysis, distal muscular weakness, joint contractures, and axial hypotonia with preserved antigravity limb movements. Phenotype overlaps considerably with SMARD type 1 but is differentiated by a mutation in a different gene.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Spinal muscular atrophy with respiratory distress type 2 | None | 2,393 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=404521 | 2021-01-23T16:52:33 | {"icd-10": ["G12.2"], "synonyms": ["Diaphragmatic spinal muscular atrophy type 2", "SMARD2", "Severe infantile axonal neuropathy with respiratory failure type 2", "X-linked spinal muscular atrophy with respiratory distress"]} |
Pitt-Hopkins-like syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by severe intellectual disability, lack of speech with normal, or mildly delayed, motor development, episodic breathing abnormalities, early-onset seizures and facial dysmorphism which only includes a wide mouth. Abnormal sleep-wake cycles, autistic behavior and stereotypic movements are commonly associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Pitt-Hopkins-like syndrome | c2750246 | 2,394 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=221150 | 2021-01-23T17:07:26 | {"gard": ["11967"], "mesh": ["C567657"], "omim": ["610042", "614325"]} |
Vitreous hemorrhage
Slit lamp photograph showing retinal detachment with visible vitreous hemorrhage.
SpecialtyOphthalmology
Vitreous hemorrhage is the extravasation, or leakage, of blood into the areas in and around the vitreous humor of the eye.[1] The vitreous humor is the clear gel that fills the space between the lens and the retina of the eye. A variety of conditions can result in blood leaking into the vitreous humor, which can cause impaired vision, floaters, and photopsia.[2]
## Contents
* 1 Symptoms
* 2 Causes
* 2.1 Diabetic retinopathy
* 2.2 Trauma
* 2.3 Retinal tear or detachment
* 2.4 Posterior vitreous detachment
* 2.5 Other causes
* 3 Diagnosis
* 4 Treatments
* 5 References
* 6 External links
## Symptoms[edit]
Common symptoms of vitreous hemorrhage include:
* Blurred vision
* Floaters – faint cobweb-like apparitions floating through the field of vision
* Reddish tint to vision
* Photopsia – brief flashes of light in the peripheral vision[2]
Small vitreous hemorrhage often manifests itself as "floaters." A moderate case will often result in dark streaks in the vision, while dense vitreous hemorrhage can significantly inhibit vision.[3]
## Causes[edit]
There are many factors known to cause vitreous hemorrhage.
### Diabetic retinopathy[edit]
The most common cause found in adults is diabetic retinopathy. Abnormal blood vessels can form in the back of the eye of a person with diabetes. These new blood vessels are weaker and prone to breaking and causing hemorrhage.[2] Diabetic retinopathy accounts for 31.5–54% of all cases of vitreous hemorrhage in adults in the United States.[1]
### Trauma[edit]
Some injuries can cause blood vessels in the back of the eye to bleed. Trauma is the leading cause of vitreous hemorrhage in young people, and accounts for 12–18.8% of cases in adults.[1]
### Retinal tear or detachment[edit]
A tear in the retina can allow fluids from the eye to leak in behind the retina, which causes retinal detachment. When this occurs, blood from the retinal blood vessels can bleed into the vitreous.[4] Retinal tear accounts for 11.4–44% of vitreous hemorrhage cases.[1]
### Posterior vitreous detachment[edit]
As one gets older, pockets of fluid can develop in the vitreous. When these pockets develop near the back of the eye, the vitreous can pull away from the retina and possibly tear it.[2] Posterior vitreous detachment accounts for 3.7–11.7% of vitreous hemorrhage cases.[1]
### Other causes[edit]
Less common causes of vitreous hemorrhage make up 6.4–18% of cases, and include:
* Proliferative sickle cell retinopathy
* Macroaneurysms
* Age-related macular degeneration
* Terson syndrome
* Retinal neovascularization as a result of branch or central retinal vein occlusion
* Other
## Diagnosis[edit]
Vitreous hemorrhage is diagnosed by identifying symptoms, examining the eye, and performing tests to identify the cause. Some common tests include:
* Examination of the eye with a microscope
* Pupil dilation and examination
* An ultrasound examination may be used if the doctor does not have a clear view of the back of the eye
* Blood tests to check for specific causes such as diabetes
* A CT scan to check for injury around the eye
* Referral to a retinal specialist[2]
## Treatments[edit]
The treatment method used depends on the cause of the hemorrhage. In most cases, the patient is advised to rest with the head elevated 30–45°, and sometimes to put patches over the eyes to limit movement prior to treatment in order to allow the blood to settle. The patient is also advised to avoid taking medications that cause blood thinning (such as aspirin or similar medications).
The goal of the treatment is to fix the cause of the hemorrhage as quickly as possible. Retinal tears are closed by laser treatment or cryotherapy, and detached retinas are reattached surgically.[5]
Even after treatment, it can take months for the body to clear all of the blood from the vitreous.[2] In cases of vitreous hemorrhage due to detached retina, long-standing vitreous hemorrhage with a duration of more than 2–3 months, or cases associated with rubeosis iridis or glaucoma, a vitrectomy may be necessary to remove the standing blood in the vitreous.
## References[edit]
1. ^ a b c d e "Vitreous Hemorrhage: Background, Pathophysiology, Epidemiology". 20 October 2019. Retrieved 5 November 2019 – via eMedicine. Cite journal requires `|journal=` (help)
2. ^ a b c d e f Garibaldi, Daniel. "Vitreous Hemorrhage." CRS – Eye Advisor (2010): 1. Health Source – Consumer Edition. Web. 29 November 2011.
3. ^ "Vitreous Hemorrhage Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 5 November 2019.
4. ^ "Retinal detachment: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 5 November 2019.
5. ^ "Vitreous Hemorrhage Treatment & Management: Medical Care, Surgical Care, Consultations". 20 October 2019. Retrieved 5 November 2019 – via eMedicine. Cite journal requires `|journal=` (help)
## External links[edit]
Classification
D
* ICD-10: H43.1
* ICD-9-CM: 379.23
* MeSH: D014823
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Vitreous hemorrhage | c0042909 | 2,395 | wikipedia | https://en.wikipedia.org/wiki/Vitreous_hemorrhage | 2021-01-18T18:56:44 | {"mesh": ["D014823"], "umls": ["C0042909"], "icd-9": ["379.23"], "icd-10": ["H43.1"], "wikidata": ["Q1529650"]} |
A rare head and neck tumor characterized by a malignant epithelial neoplasm with evidence of squamous differentiation, most commonly located in the supraglottis or glottis. The tumor can spread directly to adjacent structures or metastasize via lymphatic and blood vessels to regional lymph nodes, or lung, liver, and bones, respectively. Primary risk factors are tobacco smoking and (to a lesser extent) alcohol consumption. Patients may present with hoarseness, dyspnea, stridor, dysphagia, hemoptysis, or odynophagia.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Squamous cell carcinoma of the larynx | c1168401 | 2,396 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=494550 | 2021-01-23T16:57:17 | {"mesh": ["D000077195"], "omim": ["275355"]} |
## Summary
### Clinical characteristics.
The FLNB disorders include a spectrum of phenotypes ranging from mild to severe. At the mild end are spondylocarpotarsal synostosis (SCT) syndrome and Larsen syndrome; at the severe end are the phenotypic continuum of atelosteogenesis types I (AOI) and III (AOIII) and Piepkorn osteochondrodysplasia (POCD).
SCT syndrome is characterized by postnatal disproportionate short stature, scoliosis and lordosis, clubfeet, hearing loss, dental enamel hypoplasia, carpal and tarsal synostosis, and vertebral fusions.
Larsen syndrome is characterized by congenital dislocations of the hip, knee, and elbow; clubfeet (equinovarus or equinovalgus foot deformities); scoliosis and cervical kyphosis, which can be associated with a cervical myelopathy; short, broad, spatulate distal phalanges; distinctive craniofacies (prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes); vertebral anomalies; and supernumerary carpal and tarsal bone ossification centers. Individuals with SCT syndrome and Larsen syndrome can have midline cleft palate and hearing loss.
AOI and AOIII are characterized by severe short-limbed dwarfism; dislocated hips, knees, and elbows; and clubfeet. AOI is lethal in the perinatal period. In individuals with AOIII, survival beyond the neonatal period is possible with intensive and invasive respiratory support.
Piepkorn osteochondrodysplasia (POCD) is a perinatal-lethal micromelic dwarfism characterized by flipper-like limbs (polysyndactyly with complete syndactyly of all fingers and toes, hypoplastic or absent first digits, and duplicated intermediate and distal phalanges), macrobrachycephaly, prominant forehead, hypertelorism, and exophthalmos. Occasional features include cleft palate, omphalocele, and cardiac and genitourinary anomalies. The radiographic features at mid-gestation are characteristic.
### Diagnosis/testing.
The diagnosis of SCT is established in a proband by identification of biallelic pathogenic variants in FLNB on molecular genetic testing. The diagnosis of other FLNB disorders (Larsen syndrome, AOI, AOIII, and Piepkorn osteochondrodysplasia) is established in a proband by identification of a heterozygous pathogenic variant in FLNB on molecular genetic testing.
### Management.
Treatment of manifestations: Cervical spine instability in asymptomatic infants can be successfully managed with posterior arthrodesis. Function can be stabilized (if not improved) in infants with myelopathic signs by a combination of anterior decompression and circumferential arthrodesis. Hip dislocation in individuals with Larsen syndrome usually requires operative reduction. Scoliosis and clubfeet are managed in a routine manner. Anesthetic agents that exhibit more rapid induction and recovery are preferred in those with laryngotrachiomalacia. When possible, cleft palate and hearing loss are best managed by multidisciplinary teams.
Surveillance: Annual orthopedic evaluation for progressive scoliosis. Feeding and growth assessment for those with cleft palate by a multidisciplinary team; annual audiologic and dental evaluations.
Pregnancy management: Delivery of an affected infant has the potential to be complicated by extended breech presentation due to dislocation of the hips and knees.
### Genetic counseling.
AOI, AOIII, Piepkorn osteochondrodysplasia, and Larsen syndrome are inherited in an autosomal dominant manner. The proportion of autosomal dominant FLNB disorders caused by de novo pathogenic variants is unknown, although the vast majority of lethal FLNB conditions are caused by de novo events. In rare instances, a parent with low-level mosaicism transmits the causative pathogenic variant to an affected offspring. Each child of an individual with an autosomal dominant FLNB disorder has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk for autosomal dominant FLNB disorders is possible if the pathogenic variant in the family is known.
SCT syndrome is inherited in an autosomal recessive manner. At conception, each sib of an individual with SCT syndrome has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for SCT syndrome are possible once the pathogenic variants have been identified in the family.
## Diagnosis
Formal diagnostic criteria for FLNB disorders have not been established.
### Suggestive Findings
The FLNB disorders include a spectrum of phenotypes ranging from mild to severe. At one end are spondylocarpotarsal synostosis (SCT) syndrome and Larsen syndrome and at the severe end are the phenotypic continuum of atelosteogenesis type I (AOI) and type III (AOIII) and Piepkorn osteochondrodysplasia.
#### Spondylocarpotarsal Synostosis Syndrome
Spondylocarpotarsal synostosis (SCT) syndrome should be suspected in individuals with the following clinical and radiographic features [Langer et al 1994].
Clinical features
* Postnatal disproportionate short stature
* Scoliosis, lordosis
* Clubfeet
* Other manifestations: midline cleft palate, conductive and sensorineural hearing loss, joint stiffness, dental enamel hypoplasia
Radiographic features
* Fusion of adjacent vertebrae and posterior elements that can involve noncontiguous areas of the cervical, thoracic, and lumbar spine
Note: (1) Asymmetric fusion of the posterior elements can result in "a unilateral unsegmented vertebral bar." (2) More complex bilateral and midline-fused structures have also been reported. (3) Although frequently referred to as "segmentation defects," the process of segmentation is normal in SCT syndrome and the fusion of adjacent vertebral elements relates to a defect in a separate morphologic process that occurs later in development. (4) Basilar impression with or without foramen magnum stenosis have been recurrently observed.
* Carpal and tarsal synostosis. Carpal synostosis is usually capitate-hamate and lunate-triquetrum [Langer et al 1994].
* Delayed ossification of epiphyses (especially of carpal bones) and bilateral epiphyseal dysplasia of the femur; reported in two individuals [Honeywell et al 2002, Mitter et al 2008]
#### Larsen Syndrome
Larsen syndrome should be suspected in individuals with the following clinical and radiographic features [Larsen et al 1950].
Clinical features
* Congenital dislocations of the hip, knee, elbow, and (occasionally) shoulder
* Clubfeet (equinovarus or equinovalgus foot deformities). This may be the only clinically apparent sign in some individuals [Yang et al 2016].
* Scoliosis and cervical kyphosis, which can be associated with a cervical myelopathy
* Short, broad, spatulate distal phalanges, particularly of the thumb
* Craniofacial anomalies (prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes)
* Other manifestations: midline cleft palate, hearing loss (often resulting from malformations of the ossicles)
Radiographic features in early childhood
* Vertebral anomalies: hypoplasic vertebrae, hemivertebrae, spondylolysthesis, bifid posterior processes
* Supernumerary (accessory) carpal and tarsal bone ossification centers; possibly a universal finding [Bicknell et al 2007]
#### Atelosteogenesis Type I
Atelosteogenesis type I (AOI) should be suspected in individuals with the following clinical and radiographic features.
Clinical features
* Perinatal lethal short-limbed dwarfism
* Severe, dislocated hips, knees, and elbows; clubfeet
Radiographic features
* Marked platyspondyly
* Hypoplastic pelvis
* Thoracic hypoplasia
* Incomplete or absent, shortened, or distally tapered humeri and femora; absent, shortened, or bowed radii; shortened and bowed ulnae and tibiae; absent fibulae
* Unossified or partially ossified metacarpals and middle and proximal phalanges
* Occasionally, extraskeletal manifestations including encephalocele and omphalocele [Bicknell et al 2005]
Note: Individuals with a diagnosis of boomerang dysplasia (perinatal-lethal bone dysplasia with close similarities to AOI) are probably now best subsumed under a diagnosis of AOI. Bowing of the femora was previously considered a differentiating feature between these two conditions but following the definition of their molecular pathogenesis, it is unlikely that this clinical sign adequately differentiates two distinct conditions.
#### Piepkorn Osteochondrodysplasia
Piepkorn osteochondrodysplasia (POCD) should be suspected in individuals with the following clinical and radiographic features.
Clinical features
* Perinatal-lethal micromelic dwarfism with flipper-like limbs
* Polysyndactyly. Complete syndactyly of all fingers and toes with missing or hypoplastic thumbs and halluces. The intermediate and distal phalanges of all fingers are duplicated, resulting in distal octodactyly.
* Pronounced cranofacial dysmorphism including macrobrachycephaly, prominant forehead, hypertelorism, and exophthalmos
* Other manifestations: Cleft palate, omphalocele, cardiac and genitourinary defects
Radiographic features (at 15-21 weeks' gestation). Absent ossification of all long bones, vertebrae, pelvis, metacarpals, and metatarsals. Some ossification of the pubic bones, pedicles, ribs, scapulae, skull, and clavicles can be observed.
#### Atelosteogenesis Type III
Clinical features
* Milder than AOI; survival beyond the neonatal period is possible with intensive and invasive respiratory support [Schultz et al 1999].
* Laryngotracheobronchomalacia
* Dislocated hips, knees, and elbows; clubfeet
Radiographic features
* Mild vertebral hypoplasia
* Distal tapering of the humeri and femora
* Short and broad tubular bones of the hands and feet
### Establishing the Diagnosis
The diagnosis of SCT is established in a proband by identification of biallelic pathogenic variants in FLNB on molecular genetic testing (see Table 1).
The diagnosis of other FLNB disorders (Larsen syndrome, AOI, POCD, and AOIII) is established in a proband by identification of a heterozygous pathogenic variant in FLNB on molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing (chromosomal microarray analysis, exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of FLNB disorders is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with skeletal dysplasia and/or joint dislocations are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic and laboratory findings suggest the diagnosis of FLNB disorders, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:
* Single-gene testing. Sequence analysis of FLNB detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found (or only one pathogenic variant is identified in a proband with features characteristic of SCT syndrome), perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.
Note: To date, such variants have not been identified as a cause of Larsen syndrome, AOI, POCD or AOIII. Multiexon FLNB deletions have been identified in two individuals with SCT syndrome (see Table 1).
* A multigene panel that includes FLNB and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the phenotype is indistinguishable from many other skeletal dysplasias, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
If exome sequencing is not diagnostic – and particularly when evidence supports autosomal dominant inheritance – exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.
Note: To date such variants have not been identified as a cause of Larsen syndrome, AOI, POCD, or AOIII. Multiexon FLNB deletions have been identified in two individuals with SCT syndrome (see Table 1).
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in FLNB Disorders
View in own window
Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
FLNBSequence analysis 3<100% 4
Gene-targeted deletion/duplication analysis 5See footnote 6.
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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\.
Data derived from Human Gene Mutation Database [Stenson et al 2017]
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\.
To date deletions/duplications have not been identified as a cause of Larsen syndrome, AOI, POCD, or AOIII. Two individuals with SCT have been found to have homozygous large multiexon deletions of FLNB [Author, unpublished data].
## Clinical Characteristics
### Clinical Description
To date, more than 100 individuals with a pathogenic variant(s) in FLNB have been identified [Daniel et al 2012, Stenson et al 2017, Salian et al 2018]. The following description of the phenotypic features associated with FLNB conditions is based on these reports.
#### Spondylocarpotarsal Synostosis (SCT) Syndrome
Individuals with SCT syndrome have normal or near-normal birth length; however, progressive vertebral fusion results in poor growth of the trunk and short stature becomes evident postnatally. Stature is typically 3-6 SD below the mean.
Scoliosis is common, but variable in severity and time of onset because of the extent and pattern of vertebral fusion. Some authors have observed deformity at birth, although the phenotype may only become evident later in childhood. The irregular nature of the vertebral anomalies can also give rise to other complications such as cervical spine instability [Seaver & Boyd 2000] and basilar impression.
Clubfeet, pes planus, and cleft palate have been described in a small number of individuals with SCT syndrome. Some authors have reported mild craniofacial dysmorphism as part of this condition but the majority of individuals with SCT syndrome do not exhibit these features.
SCT syndrome has been associated with retinal anomalies [Steiner et al 2000] and sensorineural deafness [Langer et al 1994, Coêlho et al 1998]. The cataracts and retinal abnormalities described in one family with SCT syndrome were not severe enough to impair vision [Steiner et al 2000] and have not been observed in subsequently described individuals and so may not represent primary manifestations of the condition.
Dental enamel hypoplasia has been reported in at least two unrelated instances [Mitter et al 2008].
Intelligence is normal.
#### Larsen Syndrome
Larsen syndrome is compatible with survival into adulthood [Bicknell et al 2007]. Intelligence is normal.
Intrafamilial variation in Larsen syndrome can be remarkable. In a large family segregating one of the recurring pathogenic variants leading to Larsen syndrome, some individuals had cleft palate and multiple large joint dislocations, whereas others who had no major anomalies had short stature and very mild clinical and radiographic features, such as short distal phalanges and supernumerary carpal and tarsal bones [Bicknell et al 2007]. Clinical variability can also result from the presence of somatic mosaicism for a causative pathogenic variant in a mildly affected parent and the presence of a germline pathogenic variant in more severely affected offspring.
In their study of 20 unrelated families with a total of 52 affected individuals, Bicknell et al [2007] determined that all probands had dislocations or subluxations of the large joints (80% hip, 80% knee, and 65% elbow). The most mildly affected proband had subluxation of the shoulders as her only large joint manifestation. Clubfoot was present in 75% of affected individuals.
Stature is mildly affected. In 14 of 20 probands height was below the tenth centile; height was rarely below the first centile and in one individual was above the 97th centile [Bicknell et al 2007].
Spinal abnormalities were observed on x-rays in 16 (84%) of 19 probands. Cervical kyphosis was noted in 50%, usually from subluxation or fusion of the bodies of C2, C3, and C4, which was commonly associated with posterior vertebral arch dysraphism (i.e., dysplasia of the vertebral laminae and hypoplasia of the lateral processes of all cervical vertebrae). Individuals with Larsen syndrome and cervical spine dysplasia are at significant risk for cervical cord myelopathy and secondary tetraparesis [Bicknell et al 2007]. The incidence of myelopathy is at least 15%. Evidence suggests that preemptive posterior stabilization of the cervical spine in individuals with Larsen syndrome with cervical spine dysplasia may prevent this complication and that combined anterior and posterior stabilization can lead to clinical improvement in individuals with evidence of myelopathy [Sakaura et al 2007].
Craniofacial anomalies are found in all individuals with FLNB Larsen syndrome. These include a prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes. Cleft palate occurs in 15% of affected individuals.
Deafness is common [Herrmann et al 1981, Stanley et al 1988, Maack & Muntz 1991]. Conductive deafness, often with malformation of the ossicles of the middle ear, was observed in four (21%) of 19 probands [Bicknell et al 2007].
Although laryngotracheomalacia has been reported in association with Larsen syndrome, few individuals with Larsen syndrome and a documented FLNB pathogenic variant are severely affected.
Short, broad, spatulate distal phalanges, particularly of the thumb, are a common (67%; Bicknell et al [2007]) but not invariable manifestation of Larsen syndrome.
#### Atelosteogenesis Type I (AOI) / Boomerang Dysplasia
On prenatal ultrasound examination, the findings of boomerang dysplasia and AOI consist of thoracic hypoplasia and limb shortening with delayed or absent ossification of vertebral and appendicular elements. Joint dislocations may be evident. Definitive diagnosis by ultrasound examination alone is possible [Tsutsumi et al 2012]. Polyhydramnios can complicate the pregnancy. Neonates with boomerang dysplasia or AOI die soon after birth from cardiorespiratory insufficiency. Occasionally, extraskeletal manifestations including encephalocele and omphalocele are encountered [Bicknell et al 2005].
#### Atelosteogenesis Type III (AOIII)
The most conspicuous finding of AOIII is joint dislocations. A specific diagnosis of AOIII is seldom possible by prenatal ultrasound examination alone.
Infants with AOIII can survive the neonatal period but may require intensive and invasive support to do so. The infant reported by Schultz et al [1999] had significant problems with respiratory insufficiency as a result of laryngotracheomalacia and thoracic hypoplasia. Her mother, who was intellectually normal, had similar but milder respiratory problems in the neonatal period. The manifestations of AOIII overlap with those of Larsen syndrome: large joint dislocations, club feet, short stature, and spinal anomalies. The observation of a distally tapering humerus on x-ray is indicative of AOIII, and of a stronger likelihood of significant laryngotracheobronchomalacia, the major differentiating feature between these two diagnoses.
Infants with AOIII have been born to parents with milder phenotypes (similar to Larsen syndrome). In these instances, the parents probably have a mild phenotype associated with somatic mosaicism, whereas their offspring with a non-mosaic germline pathogenic variant have a severe phenotype.
Neurodevelopment is mildy affected in some long-term survivors with AOIII [Schultz et al 1999], although the authors assumed this to be a secondary consequence of orthopedic and respiratory complications of the primary disorder.
#### Piepkorn Osteochondrodysplasia (POCD)
POCD is a form of perinatal-lethal micromelic dwarfism described in fewer than five individuals in the literature. The condition is characterized by flipper-like limbs, a characteristic form of polysyndactyly with complete syndactyly of all fingers and toes. The thumbs and halluces are either hypoplastic or absent. The intermediate and distal phalanges of all fingers are duplicated, resulting in distal octodactyly. Craniofacial features include macrobrachycephaly, prominant forehead, hypertelorism, and exophthalmos. Occasional features include cleft palate, omphalocele, cardiac anomalies, and genitourinary defects including sex reversal. The radiographic features of POCD at mid-gestation are characteristic: absent ossification of all long bones, vertebrae, pelvis, metacarpals, and metatarsals. Some ossification of the pubic bones, pedicles, ribs, scapulae, skull, and clavicles can be observed.
### Genotype-Phenotype Correlations
SCT syndrome. Homozygosity or compound heterozygosity for pathogenic frameshift or nonsense variants in FLNB causes SCT syndrome [Krakow et al 2004]. Pathogenic variants associated with SCT syndrome are associated with loss of protein expression and hence constitute true null alleles [Farrington-Rock et al 2006].
Larsen syndrome, AOI, and AOIII. The pathogenic variants associated with Larsen syndrome, AOI, and AOIII are either missense variants or small in-frame deletions and are predicted to encode full-length filamin B protein.
* Larsen syndrome-associated pathogenic variants are spread predominantly over exons 2-5 and 27-33 [Bicknell et al 2007, Daniel et al 2012].
* Atelosteogenesis type III-causing pathogenic variants occur in exons 2-5, 13, and 27-33 [Farrington-Rock et al 2006].
* The large majority of pathogenic variants reported in boomerang dysplasia and AOI are in exons 2-5 [Bicknell et al 2005, Daniel et al 2012].
In some instances the same pathogenic variant is associated with different phenotypes (e.g., c.502G>A (p.Gly168Ser) is associated with both AOI and AOIII).
Recurrent pathogenic variants:
* c.5071G>A (p.Gly1691Ser) is the most common recurrent substitution, associated with phenotypes ranging from mild Larsen syndrome (isolated bilateral dislocation of the knees and digital and craniofacial anomalies) to AOIII [Bicknell et al 2005, Farrington-Rock et al 2006].
* c.679G>A (p.Glu227Lys) is associated with Larsen syndrome.
Peipkorn dysplasia. Three individuals with Peipkorn dysplasia have had pathogenic variants in exons 28 and 29.
#### Mosaicism
Clinical evidence suggests that somatic mosaicism can complicate the presentation of these conditions [Petrella et al 1993, Bicknell et al 2007, Bernkopf et al 2017]. Most notably, somatic mosaicism for an FLNB pathogenic variant can be associated with Larsen syndrome, whereas the same pathogenic variant in the germline state can be associated with AOIII.
### Penetrance
Germline FLNB pathogenic variants are fully penetrant but show variable expressivity, leading to the range of phenotypes described in this GeneReview.
### Nomenclature
Larsen syndrome. Some authors described what appeared to be autosomal recessive Larsen syndrome [Clayton-Smith & Donnai 1988, Bonaventure et al 1992, Laville et al 1994, Yamaguchi et al 1996]. Some of these families had sib recurrence of Larsen syndrome as a result of germline mosaicism in an unaffected parent [Petrella et al 1993].
In contrast, other recessive disorders with multiple joint dislocations called Larsen syndrome in the past but not sharing other clinical characteristics of Larsen syndrome are best not referred to as Larsen syndrome [Topley et al 1994]. These conditions include a variety of chondrodysplasias with multiple joint dislocations and include: the "Reunion Island form of Larsen syndrome" [Bonaventure et al 1992, Laville et al 1994], which is clinically and radiographically distinct from FLNB Larsen syndrome and caused by pathogenic variants in B4GALT7 [Cartault et al 2015]; CHST3-type chondrodysplasia; and two different forms of Desbuquois dysplasia caused by pathogenic variants in CANT1 and XYLT1.
Atelosteogenesis types I and III were so named because the major manifestation is disordered and incomplete ossification of the skeleton [Maroteaux et al 1982, Sillence et al 1982, Stern et al 1990].
Note: Atelosteogenesis type II, one of the sulfate transporter-related osteochondrodysplasias caused by pathogenic variants in SLC26A2 (DTDST), is genetically distinct from AOI and AOIII.
Piepkorn osteochondrodysplasia, although formerly considered to be the same as boomerang dysplasia, has been readdressed by Rehder et al [2018]. A case series of four indicates that a phenotype distinct from boomerang dysplasia and AOI constituting flipper-like limbs, a characteristic form of synpolydactyly, and completely absent ossification of many skeletal elements at mid-gestation defines this entity, a suggestion that is supported by a different distribution of pathogenic variants compared to those underlying boomerang dysplasia and AOI.
### Prevalence
No prevalence figures are available for any of the FLNB conditions.
## Differential Diagnosis
### Spondylocarpotarsal Synostosis (SCT) Syndrome
### Table 2.
Genes of Interest in the Differential Diagnosis of Spondylocarpotarsal Synostosis (SCT) Syndrome
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Gene(s)Differential Diagnosis DisorderMOIClinical Features
OverlappingDifferentiating
DLL3
HES7
LFNG
MESP2
RIPPLY2
TBX6Spondylocostal dysplasia (see Spondylocostal Dysostosis, AR)AR
(AD) 1Vertebral dysplasiaRib anomalies in spondylocostal dysplasia
FGF9
GDF5
NOGMultiple synostosis (OMIM PS186500)ADVertebral dysplasiaProgressive symphalangism & distinct facial findings in multiple synostosis
GDF6Klippel-Feil syndrome 1 (OMIM 118100)ADVertebral, carpal, & tarsal fusions similar to findings in SCT syndromeNo carpal or tarsal fusions. Isolated cervical fusions do not occur in SCT syndrome.
MYH3Contractures, pterygia, & variable skeletal fusions syndrome 1A (OMIM 178110)ADVertebral, carpal, & tarsal fusions similar to findings in SCT syndromePterygia can be present in individuals w/MYH3 pathogenic variant(s).
Contractures, pterygia, & variable skeletal fusions syndrome 1B (OMIM 618469)ARVertebral, carpal, & tarsal fusions similar to findings in SCT syndrome
AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance
1\.
TBX6-related spondylocostal dysplasia can be inherited in an autosomal dominant or autosomal recessive manner.
### Larsen Syndrome
### Table 3.
Genes of Interest in the Differential Diagnosis of Larsen Syndrome
View in own window
GeneDifferential Diagnosis DisorderMOIClinical Features
OverlappingDifferentiating
B3GAT3B3GAT3 deficiency (OMIM 245600)ARJoint dislocationsBrachydactyly & cardiac defects (incl bicuspid aortic valve & dilatation of the aorta) in B3GAT3 deficiency
B4GALT7Ehlers-Danlos syndrome, spondylodysplastic type 1 (OMIM 130070)ARJoint dislocationsShort stature (< -3 SD) in Ehlers-Danlos syndrome, spondylodysplastic type 1
CANT1Desbuquois dysplasia (OMIM 251450)ARJoint dislocationsShort stature (< -3 SD); advanced carpal bone age; & characteristic radiographic manifestations in hips, pelvis, & hands in Desbuquois dysplasia
CHST3CHST3 skeletal dysplasia 1ARJoint dislocationsEpiphyseal dysplasia; progressive spondylodysplasia in early & mid-childhood; rhizomelic shortening of limbs; & short stature in CHST3 skeletal dysplasia
FLNAOtopalatodigital syndrome type 1 (OPD1; see XL Otopalatodigital Spectrum Disorders)XLSpatulate fingers; craniofacial dysmorphismOPD1 is not assoc w/: dislocation of the large joints (except of the radial heads), cervical spine dysplasia, or radiologically supernumerary ossification centers w/in the carpus &/or tarsus.
GZF1Joint laxity, short stature, & myopia (JLSM; OMIM 617662)ARJoint dislocationsMyopia, short stature, & excessive joint laxity in GZF1-JLSM (seldom a characteristic of FLNB Larsen syndrome)
BPNT2
(IMPAD1)Chondrodysplasia w/joint dislocations, GPAPP type (GPAPP deficiency) (OMIM 614078)ARJoint dislocationsPronounced brachydactyly, asymmetry in the hands, & short stature in GPAPP deficiency
AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked
1\.
Also known as spondyloepiphyseal dysplasia, Omani type.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with an FLNB disorder, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 4.
Recommended Evaluations Following Initial Diagnosis in Individuals with FLNB Disorders
View in own window
System/ConcernEvaluationComment
OrthopedicLateral cervical spine films in flexion & extension
* To evaluate for cervical dysplasia, which can → cervical cord myelopathy
* Evaluate cervical spine for instability prior to general anesthesia.
Spine filmsTo evaluate for vertebral abnormalities that predispose to scoliosis
Clinical & ultrasound assessment of hips for dislocationDevelopment of dislocations postnatally has not been described.
Clinical examination for joint dislocation, club foot
ENTEvaluation for cleft palate
PulmonologyRespiratory examinationFor evidence of laryngotracheobronchomalacia
AudiologyAudiologic evaluationTo assess for sensorineural &/or conductive hearing loss
OphthalmologyOphthalmologic examinationIn those w/SCT syndrome to evaluate for retinal anomalies
DentalEvaluation for enamel hypoplasia & need for sealants
OtherConsultation w/clinical geneticist &/or genetic counselor
### Treatment of Manifestations
### Table 5.
Treatment of Manifestations in Individuals with FLNB Disorders
View in own window
Manifestation/
ConcernTreatmentConsiderations/Other
Cervical spine
instability
* Asymptomatic infants: Early intervention to improve cervical spine stability using posterior arthrodesis is successful.
* Infants w/myelopathic signs: Function can be stabilized &/or improved by combination of anterior decompression & circumferential arthrodesis. 1
Care must be taken to minimize extension of cervical spine intraoperatively.
ScoliosisMedical treatment per orthopedistNo effective surgical intervention has been described.
Large joint
dislocationsOperative reduction is usually required.Conservative, nonsurgical management of hip dislocation in Larsen syndrome is often unsuccessful.
ClubfeetRoutine management per orthopedist
Laryngotrach-eomalaciaAnesthetic agents that exhibit more rapid induction & recovery are preferred.Due to ↑ risk for airway complications in individuals w/Larsen syndrome
Cleft palateTreated by multidisciplinary craniofacial team when possible
Hearing lossPossible treatments incl: hearing aids, vibrotactile devices, & cochlear implantation (see Hereditary Hearing Loss and Deafness Overview).
* Ideally, by ENT & audiologist w/expertise in early-childhood otologic disorders
* The expertise of an educator of the Deaf may be required. An important part of evaluation is determining appropriate habilitation option.
1\.
Johnston et al [1996], Sakaura et al [2007], Madera et al [2008]
### Surveillance
### Table 6.
Recommended Surveillance for Individuals with FLNB Disorders
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System/ConcernEvaluationFrequency
Vertebral anomaliesOrthopedic evaluation for development of progressive scoliosisAnnually from birth
Feeding for those w/cleftFeeding & growth assessmentAs per multidisciplinary craniofacial team
AudiologyAudiology examinationAnnually
Enamel hypoplasiaDental evaluation
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Delivery of an affected infant has the potential to be complicated by extended breech presentation due to dislocation of the hips and knees.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| FLNB Disorders | None | 2,397 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK2534/ | 2021-01-18T21:27:24 | {"synonyms": []} |
Wandering spleen
Other namesPelvic spleen, displaced spleen, drifting spleen, splenoptosis, floating spleen, splenic ptosis
A picture of an enlarged spleen taken using medical ultrasonography.
SpecialtyAngiology
Wandering spleen (or pelvic spleen) is a rare medical disease caused by the loss or weakening of the ligaments that help to hold the spleen stationary.[1]
## Contents
* 1 Symptoms and signs
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 Prevalence
* 6 Culture
* 7 References
* 8 External links
## Symptoms and signs[edit]
Symptoms include an enlargement in the size of the spleen,[2] or a change from the spleen's original position to another location, usually in either other parts of the abdomen or into the pelvis. This ability to move to other locations is commonly attributed to the spleen's pedicle being abnormally long.[3]
Physical factors may cause ischuria, constipation, as well as numerous spleen-related diseases such as hypersplenism, thrombocytopenia, and lymphoma.[4] Blocking of the arteries and torsion in the spleen can also result in abdominal pain or swelling.[5] However, lack of visible symptoms — except in incidents of abdominal pain — makes the disease difficult for doctors to diagnose,[6] though medical imaging techniques such as medical ultrasonography, magnetic resonance imaging, or computed tomography can be used to confirm its occurrence. Characteristics of the disorder include the loss, weakening, or malformation of the ligaments[2] that help to keep the spleen located in the upper left part of the abdomen.[citation needed]
## Cause[edit]
Though not a genetic disease, wandering spleen is often found at birth. It can occur in adults as the result of injuries and other similar conditions that cause the ligaments to weaken, such as connective tissue disease or pregnancy.[2] Wandering spleen (splenoptosis) predisposes the spleen to complications such as torsion, splenic infarction, pancreatic necrosis and rarely pseudocyst formation.[7]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (February 2018)
## Treatment[edit]
The usual treatment is splenopexy, fixation of the spleen, but if there is no blood flow after unwinding the spleen through detorsion then splenectomy must be performed.[6] Although there have been few reported cases of treatment through laparoscopic surgery due to the rarity of the disease, it has been proven to be an effective surgical technique.[8]
## Prevalence[edit]
Wandering spleen is most commonly diagnosed in young children[3] as well as women between the ages of 20 and 40.[6] Even so, the disease is very rare and fewer than 500 occurrences of the disease have been reported as of 2005,[3] of which around 148 (including both children and adult cases) were documented to have been from between 1960 and 1992.[4] Less than 0.5% of all splenectomies, surgical removal of the spleen, are performed due to having this disorder. In 1992, the youngest case of the literature of torsion of wandering spleen at two days of birth was reported in Lebanon, by Dr Edouard Sayad.[9]
## Culture[edit]
Susan Mayer on the TV show Desperate Housewives had an operation to fix her wandering spleen in Season 2 of the show.
## References[edit]
1. ^ "Wandering spleen". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. rarediseases.info.nih.gov. Retrieved 2018-04-17.
2. ^ a b c "Wandering Spleen". NORD. Retrieved 2007-02-25.
3. ^ a b c Hasan Alawi, Malak; Ahmad Khalifa; Sami Hassan Bana (October–December 2005). "Wandering Spleen: A Challenging Diagnosis" (PDF). Pakistan Journal of Medical Sciences. Open Publishing. Retrieved 2007-02-25.
4. ^ a b Satyadas T, Nasir N, Bradpiece HA (April 27, 2002). "Wandering spleen: case report and literature review". J. R. Coll. Edinb. 47 (2): 512–4. PMID 12018698.
5. ^ "Wandering spleen". Archived from the original on 2012-02-05. Retrieved 2007-02-26.
6. ^ a b c Safioleas MC, Stamatakos MC, Diab AI, Safioleas PM (January 2007). "Wandering spleen with torsion of the pedicle". Saudi Med J. 28 (1): 135–6. PMID 17206307.
7. ^ M, Noushif (Jul 2011). "Splenic pseudocyst: a rare association with splenoptosis and vertebral segmentation anomalies". Singapore Med J. 52 (7): e141-2. PMID 21808945.
8. ^ Castellón-Pavón CJ, Valderrábano-González S, Anchústegui-Melgarejo P, et al. (December 2006). "[Laparoscopic splenectomy due to torsion of a wandering spleen]". Cir Esp (in Spanish). 80 (6): 406–8. doi:10.1016/s0009-739x(06)70996-4. PMID 17192227.
9. ^ Sayad E, Bouchi J, Abou Haidar A (1992). "[Volvulus of a wandering spleen on the 2nd day after birth]". Le Journal Médical Libanais. The Lebanese Medical Journal (in French). 40 (3): 163–5. PMID 1339897.
## External links[edit]
Classification
D
* ICD-9-CM: 289.59
* MeSH: D050805
* DiseasesDB: 33272
* v
* t
* e
Lymphatic disease: organ and vessel diseases
Thymus
* Abscess
* Hyperplasia
* Hypoplasia
* DiGeorge syndrome
* Ectopic thymus
* Thymoma
* Thymic carcinoma
Spleen
* Asplenia
* Asplenia with cardiovascular anomalies
* Accessory spleen
* Polysplenia
* Wandering spleen
* Splenomegaly
* Banti's syndrome
* Splenic infarction
* Splenic tumor
Lymph node
* Lymphadenopathy
* Generalized lymphadenopathy
* Castleman's disease
* Intranodal palisaded myofibroblastoma
* Kikuchi disease
* Tonsils
* see Template:Respiratory pathology
Lymphatic vessels
* Lymphangitis
* Lymphangiectasia
* Lymphedema
* Primary lymphedema
* Congenital lymphedema
* Lymphedema praecox
* Lymphedema tarda
* Lymphedema–distichiasis syndrome
* Milroy's disease
* Secondary lymphedema
* Bullous lymphedema
* Factitial lymphedema
* Postinflammatory lymphedema
* Postmastectomy lymphangiosarcoma
* Waldmann disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| Wandering spleen | c0272414 | 2,398 | wikipedia | https://en.wikipedia.org/wiki/Wandering_spleen | 2021-01-18T18:31:05 | {"gard": ["328"], "mesh": ["D050805"], "icd-9": ["289.59"], "wikidata": ["Q7967227"]} |
A number sign (#) is used with this entry because of evidence that susceptibility to cutaneous malignant melanoma-6 (CMM6) is conferred by variation in the XRCC3 gene (600675) on chromosome 14q32.
Description
Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010).
For a discussion of genetic heterogeneity of cutaneous malignant melanoma, see 155600.
Molecular Genetics
Exposure to UV radiation is a major risk factor for the development of malignant melanoma. DNA damage caused by UV radiation is thought to play a major role in carcinogenesis. In an investigation of the association between polymorphisms in DNA repair genes and the development of malignant melanoma, Winsey et al. (2000) studied 125 individuals with malignant melanoma lesions or staging suggesting a high risk of relapse or metastatic disease. They found that the presence of a T allele at position 18067 in exon 7 of the XRCC3 gene (600675.0001) was significantly associated with melanoma development (p = 0.004; odds ratio, 2.36; relative risk, 1.74).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
| MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 6 | c2314896 | 2,399 | omim | https://www.omim.org/entry/613972 | 2019-09-22T15:56:59 | {"omim": ["613972"], "orphanet": ["618"]} |
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