{"action":"created","comment":{"url":"https://api.github.com/repos/alexbaumgertner/life/pulls/comments/25568049","id":25568049,"diff_hunk":"@@ -0,0 +1,169 @@\n+\n+'''Hereditary hemorrhagic telangiectasia''' (HHT), also known as '''Osler–Weber–Rendu disease''' and '''Osler–Weber–Rendu syndrome''', is an autosomal dominant [[genetic disorder]] that leads to abnormal blood vessel formation in the [[Human skin|skin]], [[mucous membrane]]s, and often in organs such as the [[lung]]s, [[liver]], and [[brain]].<ref name=Shovlin/><ref name=Dupuis/>\n+\n+It may lead to [[epistaxis|nosebleeds]], [[Gastrointestinal bleeding|acute and chronic digestive tract bleeding]], and various problems due to the involvement of other organs. Treatment focuses on reducing bleeding from blood vessel lesions, and sometimes [[surgery]] or other targeted interventions to remove [[arteriovenous malformation]]s in organs. Chronic bleeding often requires [[iron supplements]] and sometimes [[blood transfusion]]s. HHT is transmitted in an [[Dominance (genetics)|autosomal dominant]] fashion, and occurs in one in 5,000 people.<ref name=Shovlin/><ref name=Dupuis/>\n+\n+The disease carries the names of Sir [[William Osler]], [[Henri Jules Louis Marie Rendu]], and [[Frederick Parkes Weber]], who described it in the late 19th and early 20th centuries.<ref name=Fuchizaki/>\n+\n+==Признаки и симптромы==\n+===Телеангиэктазии===\n+[[Image:TongueTelang.JPG|thumb|Tongue telangiectases as seen in a person with hereditary hemorrhagic telangiectasia]]\n+[[Telangiectasia]] (small vascular malformations) may occur in the skin and mucosal linings of the nose and gastrointestinal tract. The most common problem is [[epistaxis|nosebleeds]] (epistaxis), which happen frequently from childhood and affect about 90–95% of people with HHT. Lesions on the skin and in the mouth bleed less often but may be considered cosmetically displeasing; they affect about 80%.<ref name=Shovlin>{{cite journal |author=Govani FS, Shovlin CL |title=Hereditary haemorrhagic telangiectasia: a clinical and scientific review |journal=European Journal of Human Genetics |volume=17 |issue=7 |pages=860–71 |date=July 2009 |pmid=19337313 |pmc=2986493 |doi=10.1038/ejhg.2009.35 |url=http://www.nature.com/ejhg/journal/v17/n7/full/ejhg200935a.html}}</ref><ref name=Dupuis>{{cite journal |author=Dupuis-Girod S, Bailly S, Plauchu H |title=Hereditary hemorrhagic telangiectasia (HHT): from molecular biology to patient care |journal=J. Thromb. Haemost. |volume= 8|issue= 7|pages= 1447–56|date=March 2010 |pmid=20345718 |doi=10.1111/j.1538-7836.2010.03860.x}}</ref> The skin lesions characteristically occur on the [[lip]]s, the [[Human nose|nose]] and the [[finger]]s, and on the skin of the face in sun-exposed areas. They appear suddenly, with the number increasing over time.<ref name=Dupuis/>\n+\n+About 20% are affected by symptomatic digestive tract lesions, although a higher percentage have lesions that do not cause symptoms. These lesions may bleed intermittently, which is rarely significant enough to be noticed (in the form of [[hematemesis|bloody vomiting]] or [[melena|black stool]]), but can eventually lead to depletion of [[iron]] in the body, resulting in [[iron-deficiency anemia]].<ref name=Shovlin/><ref name=Dupuis/>\n+\n+===Артериовенозная мальформация===\n+[[File:AVM grossly.jpg|right|thumb|A very large arteriovenous malformation in the left hemisphere (on the right in this image) of the brain.]]\n+[[Arteriovenous malformation]] (AVM, larger vascular malformations) occur in larger organs, predominantly the lungs (50%), liver (30–70%) and the [[brain]] (10%), with a very small proportion (<1%) having AVMs in the [[spinal cord]].<ref name=Shovlin/><ref name=Dupuis/>\n+\n+Vascular malformations in the lungs may cause a number of problems. The lungs normally \"filter out\" [[bacteria]] and [[thrombus|blood clots]] from the bloodstream; AVMs bypass the capillary network of the lungs and allow these to [[embolism|migrate]] to the brain, where bacteria may cause a [[brain abscess]] and blood clots may lead to [[stroke]].<ref name=Shovlin/> HHT is the most common cause of lung AVMs: out of all people found to have lung AVMs, 70–80% are due to HHT.<ref name=Gossage>{{cite journal |author=Gossage JR, Kanj G |title=Pulmonary arteriovenous malformations. A state of the art review |journal=Am. J. Respir. Crit. Care Med. |volume=158 |issue=2 |pages=643–61 |date=August 1998 |pmid=9700146 |doi= 10.1164/ajrccm.158.2.9711041|url=http://ajrccm.atsjournals.org/cgi/content/full/158/2/643}}</ref><ref name=Faughnan>{{cite journal |author=Faughnan ME, Granton JT, Young LH |title=The pulmonary vascular complications of hereditary haemorrhagic telangiectasia |journal=Eur. Respir. J. |volume=33 |issue=5 |pages=1186–94 |date=May 2009 |pmid=19407052 |doi=10.1183/09031936.00061308}}</ref> Bleeding from lung AVMs is relatively unusual, but may cause [[hemoptysis]] (coughing up blood) or [[hemothorax]] (blood accumulating in the chest cavity).<ref name=Shovlin/><ref name=Dupuis/><ref name=Gossage/> Large vascular malformations in the lung allow oxygen-depleted blood from the [[right ventricle]] to bypass the [[Pulmonary alveolus|alveoli]], meaning that this blood does not have an opportunity to absorb fresh oxygen. This may lead to [[dyspnea|breathlessness]].<ref name=Gossage/><ref name=Faughnan/> Large AVMs may lead to [[platypnea]], difficulty in breathing that is more marked when sitting up compared to lying down; this probably reflects changes in blood flow associated with positioning.<ref name=Gossage/> Very large AVMs cause a marked inability to absorb oxygen, which may be noted by [[cyanosis]] (bluish discoloration of the lips and skin), [[nail clubbing|clubbing of the fingernails]] (often encountered in chronically low oxygen levels), and a [[bruit|humming noise]] over the affected part of the lung detectable by [[stethoscope]].<ref name=Gossage/><ref name=Faughnan/>\n+\n+The symptoms produced by AVMs in the liver depend on the type of abnormal connection that they form between blood vessels. If the connection is between [[arteries]] and [[vein]]s, a large amount of blood bypasses the body's organs, for which the heart compensates by increasing the [[cardiac output]]. Eventually [[congestive cardiac failure]] develops (\"high-output cardiac failure\"), with breathlessness and leg swelling among other problems.<ref name=Shovlin/><ref name=Buscarini>{{cite journal |author=Buscarini E, Plauchu H, Garcia Tsao G, ''et al.'' |title=Liver involvement in hereditary hemorrhagic telangiectasia: consensus recommendations |journal=Liver Int. |volume=26 |issue=9 |pages=1040–6 |date=November 2006 |pmid=17032403 |doi=10.1111/j.1478-3231.2006.01340.x}}</ref> If the AVM creates a connection between the [[portal vein]] and the blood vessels of the liver, the result may be [[portal hypertension]] (increased portal vein pressure), in which collateral blood vessels form in the [[esophagus]] ([[esophageal varices]]), which may bleed violently; furthermore, the increased pressure may give rise to fluid accumulation in the abdominal cavity ([[ascites]]). If the flow in the AVM is in the other direction, portal venous blood flows directly into the veins rather than running through the liver; this may lead to [[hepatic encephalopathy]] (confusion due to portal waste products irritating the brain). Rarely, the bile ducts are deprived of blood, leading to severe [[cholangitis]] (inflammation of the bile ducts).<ref name=Shovlin/><ref name=Buscarini/> Liver AVMs are detectable in over 70% of people with HHT, but only 10% experience problems as a result.<ref name=Dupuis/>\n+\n+In the brain, AVMs occasionally exert pressure, leading to [[headache]]s. They may also increase the risk of [[seizure]]s, as would any abnormal tissue in the brain. Finally, hemorrhage from an AVM may lead to [[intracerebral hemorrhage]] (bleeding into the brain), which causes any of the symptoms of stroke such as weakness in part of the body or difficulty speaking. If the bleeding occurs into the [[subarachnoid space]] ([[subarachnoid hemorrhage]]), there is usually a [[thunderclap headache|severe, sudden headache]] and decreased level of consciousness and often weakness in part of the body.<ref name=Shovlin/><ref name=Dupuis/>\n+\n+===Другие последствия===\n+A very small proportion (those affected by ''SMAD4'' mutations, see below) have [[Juvenile polyposis syndrome|multiple benign polyps]] in the [[colon (anatomy)|large intestine]], which may bleed or transform into [[colorectal cancer]]. A similarly small proportion experiences [[pulmonary hypertension]], a state in which the [[Pulmonary artery pressure|pressure in the lung arteries]] is increased, exerting pressure on the [[right ventricle|right side of the heart]] and causing [[peripheral edema]] (swelling of the legs), [[Syncope (medicine)|fainting]] and attacks of [[chest pain]]. It has been observed that the risk of [[thrombosis]] (particularly [[venous thrombosis]], in the form of [[deep vein thrombosis]] or [[pulmonary embolism]]) may be increased. There is a suspicion that those with HHT may have a mild [[immunodeficiency]] and are therefore at a slightly increased risk from infections.<ref name=Shovlin/>\n+\n+==Генетика==\n+[[Image:Autosomal dominant - en.svg|thumb|right|Hereditary hemorrhagic telangiectasia has an autosomal dominant pattern of inheritance.]]\n+\n+HHT is a [[genetic disorder]] by definition. It is inherited in an [[autosomal dominant]] manner, which means that an affected person carries one abnormal gene with a 50% chance of passing this gene to offspring. Those with HHT symptoms that have no relatives with the disease may have a new mutation.<ref name=Guideline>{{cite journal |author=Faughnan ME, Palda VA, Garcia-Tsao G, ''et al.'' |title=International guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia |journal=Journal of Medical Genetics |volume=48 |issue=2 |pages=73–87 |year=2011 |pmid=19553198 |doi=10.1136/jmg.2009.069013}}</ref> It seems that carrying two abnormal copies of the gene is not compatible with life, and hence no homozygotes have been described.<ref name=Shovlin/>\n+\n+Five genetic types of HHT are recognized. Of these, three have been [[genetic linkage|linked]] to particular [[gene]]s, while the two remaining have currently only been associated with a particular [[locus (genetics)|locus]]. More than 80% of all cases of HHT are due to mutations in either ''ENG'' or ''ACVRL1''.<ref name=Abdalla>{{cite journal |author=Abdalla SA, Letarte M |title=Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease |journal=Journal of Medical Genetics |volume=43 |issue=2 |pages=97–110 |date=February 2006 |pmid=15879500 |pmc=2603035 |doi=10.1136/jmg.2005.030833 |url=http://jmg.bmj.com/content/43/2/97.long}}</ref> A total of over 600 different mutations is known. There is likely to be a predominance of either type in particular populations, but the data are conflicting. ''MADH4'' mutations, which cause colonic polyposis in addition to HHT, comprise about 2% of disease-causing mutations. Apart from ''MADH4'', it is not clear whether mutations in ''ENG'' and ''ACVRL1'' lead to particular symptoms,<ref name=Shovlin/> although some reports suggest that ''ENG'' mutations are more likely to cause lung problems while ''ACVRL1'' mutations may cause more liver problems,<ref name=Dupuis/><ref name=Faughnan/> and pulmonary hypertension may be a particular problem in people with ''ACVRL1'' mutations.<ref name=Abdalla/> People with exactly the same mutations may have different nature and severity of symptoms, suggesting that additional genes or other risk factors may determine the rate at which lesions develop; these have not yet been identified.<ref name=Dupuis/><ref name=Abdalla/>\n+\n+{| class=\"wikitable\"\n+|-\n+! Name\n+! [[OMIM]]\n+! Gene\n+! Locus\n+! Description\n+|-\n+| HHT1\n+| {{OMIM2|187300}}\n+| ''[[endoglin|ENG]]''\n+| [[chromosome 9|9]][http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=9q34.1 q34.1]\n+| ''ENG'' codes for endoglin, a [[receptor (biochemistry)|receptor]] of [[TGF beta 1|TGF-β1]] (''transforming growth factor beta 1'') and [[TGF beta 3|TGF-β3]]; the genetic linkage was identified in 1994.<ref name=McAllister1994>{{cite journal |author=McAllister KA, Grogg KM, Johnson DW, ''et al.'' |title=Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1 |journal=Nat. Genet. |volume=8 |issue=4 |pages=345–51 |date=December 1994 |pmid=7894484 |doi=10.1038/ng1294-345}}</ref> A high proportion of [[frameshift mutation]]s has been observed.<ref name=Shovlin/> Practically all mutations occur in the extracellular part of the protein (the part that sits on the [[cell membrane|surface of the cell]]).<ref name=Abdalla/>\n+|-\n+| HHT2\n+| {{OMIM2|600376}}\n+| ''[[ACVRL1]]''\n+| [[chromosome 12|12]][http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=12q11 q11-q14]\n+| ''ACVRL1'' codes for Alk-1 (activin receptor-like kinase 1), a TGF-β1 receptor; genetic linkage was identified in 1996.<ref name=Johnson1996>{{cite journal |author=Johnson DW, Berg JN, Baldwin MA, ''et al.'' |title=Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2 |journal=Nat. Genet. |volume=13 |issue=2 |pages=189–95 |date=June 1996 |pmid=8640225 |doi=10.1038/ng0696-189}}</ref>\n+|-\n+| HHT3\n+| {{OMIM2|601101}}\n+| ''Unknown''\n+| [[chromosome 5|5]][http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=5q31 q31]\n+| Function unknown, linkage identified in 2005.<ref>{{cite journal |author=Cole SG, Begbie ME, Wallace GM, Shovlin CL |title=A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5 |journal=Journal of Medical Genetics |volume=42 |issue=7 |pages=577–82 |year=2005 |pmid=15994879 |doi=10.1136/jmg.2004.028712 |pmc=1736109}}</ref>\n+|-\n+| HHT4\n+| {{OMIM2|610655}}\n+| ''Unknown''\n+| [[chromosome 7|7]][http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=7p14 p14].\n+| Function unknown, linkage identified in 2006.<ref>{{cite journal |author=Bayrak-Toydemir P, McDonald J, Akarsu N, ''et al.'' |title=A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7 |journal=American Journal of Medical Genetics |volume=140 |issue=20 |pages=2155–62 |year=2006 |pmid=16969873 |doi=10.1002/ajmg.a.31450}}</ref>\n+|-\n+| JPHT\n+| {{OMIM2|175050}}\n+| ''[[Mothers against decapentaplegic homolog 4|MADH4]]''\n+| [[chromosome 18|18]][http://www.ncbi.nlm.nih.gov/Omim/getmap.cgi?chromosome=18q21 q21.1]\n+| ''MADH4'' codes for SMAD4, an intracellular signalling protein for the TGF superfamily receptors. Mutations in this gene cause HHT and juvenile polyposis. Linkage was identified in 2004.<ref>{{cite journal |author=Gallione CJ, Repetto GM, Legius E, ''et al.'' |title=A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4) |journal=Lancet |volume=363 |issue=9412 |pages=852–9 |date=March 2004 |pmid=15031030 |doi=10.1016/S0140-6736(04)15732-2}}</ref> Mutations mostly in exons 8–11, often ''de novo'' (newly acquired, not inherited).<ref name=Shovlin/>\n+|}\n+\n+==Патофизиология==\n+[[Image:Endoglin and Alk1.png|right|thumb|A schematic representation of the TGF-β signaling pathway. Endoglin (yellow) is needed for signalling. The ligand (blue) binds to the receptor complex; red indicates a type II receptor protein, which activates a type I receptor protein (turquiose) such as alk-1, which in turn phosphorylates a SMAD-based nuclear transcription factor (green and purple).]]\n+Telangiectasias and arteriovenous malformations in HHT are thought to arise because of changes in [[angiogenesis]], the development of blood vessels out of existing ones. The development of a new blood vessel requires the activation and migration of various types of cells, chiefly [[endothelium]], [[smooth muscle]] and [[pericyte]]s. The exact mechanism by which the HHT mutations influence this process is not yet clear, and it is likely that they disrupt a balance between pro- and antiangiogenic signals in blood vessels. The wall of telangiectasias is unusually [[friable]], which explains the tendency of these lesions to bleed.<ref name=Shovlin/>\n+\n+All genes known so far to be linked to HHT code for proteins in the [[TGF beta signaling pathway|TGF-β signaling pathway]]. This is a group of proteins that participates in [[signal transduction]] of hormones of the [[transforming growth factor beta superfamily]] (the [[transforming growth factor beta]], [[bone morphogenetic protein]] and [[growth differentiation factor]] classes), specifically [[GDF2|BMP9/GDF2]] and [[Bone morphogenetic protein 10|BMP10]]. The hormones do not enter the cell but link to receptors on the cell membrane; these then activate other proteins, eventually influencing cellular behavior in a number of ways such as cellular survival, proliferation (increasing in number) and differentiation (becoming more specialized).<ref name=Shovlin/> For the hormone signal to be adequately transduced, a combination of proteins is needed: two each of two types of [[Serine/threonine-specific protein kinase|serine/threonine-specific kinase type]] [[membrane receptor]]s and endoglin. When bound to the hormone, the type II receptor proteins [[phosphorylation|phosphorylate]] (transfer [[phosphate]]) onto type I receptor proteins (of which Alk-1 is one), which in turn phosphorylate a complex of [[SMAD (protein)|SMAD proteins]] (chiefly [[Mothers against decapentaplegic homolog 1|SMAD1]], [[Mothers against decapentaplegic homolog 5|SMAD5]] and [[Mothers against decapentaplegic homolog 9|SMAD8]]). These bind to SMAD4 and migrate to the [[cell nucleus]] where they act as [[transcription factors]] and participate in the [[transcription (genetics)|transcription]] of particular genes. In addition to the SMAD pathway, the membrane receptors also act on the [[MAPK/ERK pathway|MAPK pathway]], which has additional actions on the behavior of cells.<ref name=Dupuis/> Both Alk-1 and endoglin are [[Gene expression|expressed]] predominantly in endothelium, perhaps explaining why HHT-causing mutations in these proteins lead predominantly to blood vessel problems.<ref name=Dupuis/><ref name=Abdalla/> Both ''ENG'' and ''ACVRL1'' mutations lead predominantly to underproduction of the related proteins, rather than misfunctioning of the proteins.<ref name=Abdalla/>\n+\n+==Диагностика==\n+Diagnostic tests may be conducted for various reasons. Firstly, some tests are needed to confirm or refute the diagnosis. Secondly, some are needed to identify any potential complications.<ref name=Guideline/>\n+\n+===Телеангиэктазии===\n+[[File:Argon plasma coagulation.jpg|right|thumb|A vascular lesion in the digestive tract, being treated with argon plasma coagulation.]]\n+The skin and oral cavity telangiectasias are visually identifiable on [[physical examination]], and similarly the lesions in the nose may be seen on [[endoscopy]] of the [[nasopharynx]] or on [[laryngoscope|laryngoscopy]]. The severity of nosebleeds may be quantified objectively using a grid-like questionnaire in which the number of nosebleed episodes and their duration is recorded.<ref name=Dupuis/>\n+\n+Digestive tract telangiectasias may be identified on [[esophagogastroduodenoscopy]] (endoscopy of the esophagus, stomach and first part of the small intestine). This procedure will typically only be undertaken if there is anemia that is more marked than expected by the severity of nosebleeds, or if there is evidence of severe bleeding (vomiting blood, black stools). If the number of lesions seen on endoscopy is unexpectedly low, the remainder of the small intestine may be examined with [[capsule endoscopy]], in which the patient swallows a capsule-shaped device containing a miniature camera which transmits images of the digestive tract to a portable digital recorder.<ref name=Dupuis/>\n+\n+===Артериовенозная мальформация===\n+Identification of AVMs requires detailed [[medical imaging]] of the organs most commonly affected by these lesions. Not all AVMs cause symptoms or are at risk of doing so, and hence there is a degree of variation between specialists as to whether such investigations would be performed, and by which modality; often, decisions on this issue are reached together with the patient.<ref name=Shovlin/>\n+\n+Lung AVMs may be suspected because of the abnormal appearance of the lungs on a [[chest radiograph|chest X-ray]], or [[hypoxia (medical)|hypoxia]] (low oxygen levels) on [[pulse oximetry]] or [[arterial blood gas]] determination. [[Transthoracic echocardiography|Bubble contrast echocardiography]] (bubble echo) may be used as a screening tool to identify abnormal connections between the [[pulmonary artery|lung arteries]] and [[pulmonary vein|veins]]. This involves the injection of agitated [[saline (medicine)|saline]] into a vein, followed by ultrasound-based imaging of the heart. Normally, the lungs remove small air bubbles from the circulation, and they are therefore only seen in the [[right atrium]] and the [[right ventricle]]. If an AVM is present, bubbles appear in the [[left atrium]] and [[left ventricle]], usually 3–10 [[cardiac cycle]]s after the right side; this is slower than in [[congenital heart defect|heart defects]], in which there are direct connections between the right and left side of the heart. A larger number of bubbles is more likely to indicate the presence of an AVM. Bubble echo is not a perfect screening tool as it can miss smaller AVMs and does not identify the site of AVMs.  Often [[radiocontrast|contrast]]-enhanced [[X-ray computed tomography|computed tomography]] (CT angiography) is used to identify lung lesions; this modality has a [[Sensitivity and specificity|sensitivity]] of over 90%.<ref name=Shovlin/><ref name=Dupuis/> It may be possible to omit contrast administration on modern CT scanners.<ref name=Faughnan/> Echocardiography is also used if there is a suspicion of pulmonary hypertension or high-output cardiac failure due to large liver lesions, sometimes followed by [[cardiac catheterization]] to measure the pressures inside the various chambers of the heart.<ref name=Shovlin/>\n+\n+[[File:Morbus-Osler-CT-Leber-ax-010.jpg|thumb|CT-scan of vascular malformations in the liver in a patient with hereditary hemorrhagic telangiectasia causing an inhomogeneous perfusion pattern.]]\n+Liver AVMs may be suspected because of abnormal [[liver function tests]] in the blood, because the symptoms of heart failure develop, or because of [[jaundice]] or other symptoms of liver dysfunction. The most reliable initial screening test is [[Medical ultrasonography#Doppler sonography|Doppler ultrasonography]] of the liver; this has a very high sensitivity for identifying vascular lesions in the liver. If necessary, contrast-enhanced CT may be used to further characterize AVMs.<ref name=Shovlin/><ref name=Dupuis/><ref name=Buscarini/> It is extremely common to find incidental nodules on liver scans, most commonly due to [[focal nodular hyperplasia]] (FNH), as these are a hundredfold times more common in HHT compared to the general population. FNH is regarded as harmless. Generally, [[tumor marker]]s and additional imaging modalities are used to differentiate between FNH and malignant tumors of the liver. [[Liver biopsy]] is discouraged in people with HHT as the risk of hemorrhage from liver AVMs may be significant.<ref name=Buscarini/><ref name=Guideline/> Liver scans may be useful if someone is suspected of HHT, but does not meet the criteria (see below) unless liver lesions can be demonstrated.<ref name=Guideline/>\n+\n+Brain AVMs may be detected on [[computed tomography angiography]] (CTA or CT angio) or [[magnetic resonance angiography]] (MRA); CTA is better in showing the vessels themselves, and MRA provides more detail about the relationship between an AVM and surrounding brain tissue.<ref name=Friedlander>{{cite journal |author=Friedlander RM |title=Clinical practice. Arteriovenous malformations of the brain |journal=N. Engl. J. Med. |volume=356 |issue=26 |pages=2704–12 |date=June 2007 |pmid=17596605 |doi=10.1056/NEJMcp067192}}</ref> In general, MRI is recommended.<ref name=Dupuis/><ref name=Guideline/> Various types of vascular malformations may be encountered: AVMs, micro-AVMs, telangiectasias and arteriovenous [[fistula]]s.<ref name=Guideline/> If surgery, embolization, or other treatment is contemplated (see below), [[cerebral angiography]] may be required to get sufficient detail of the vessels. This procedure carries a small risk of stroke (0.5%) and is therefore limited to specific circumstances.<ref name=Guideline/><ref name=Friedlander/> Recent professional guidelines recommend that all children with suspected or definite HHT undergo a brain MRI early in life to identify AVMs that can cause major complications.<ref name=Guideline/> Others suggest that screening for cerebral AVMs is probably unnecessary in those who are not experiencing any neurological symptoms, because most lesions discovered on screening scans would not require treatment, creating undesirable conundrums.<ref name=Shovlin/>\n+\n+===Генетическое тестирование===\n+Genetic tests are available for the ''ENG'', ''ACVRL1'' and ''MADH4'' mutations. Testing is not always needed for diagnosis, because the symptoms are sufficient to distinguish the disease from other diagnoses. There are situations in which testing can be particularly useful. Firstly, children and young adults with a parent with definite HHT may have limited symptoms, yet be at risk from some of the complications mentioned above; if the mutation is known in the affected parent, absence of this mutation in the child would prevent the need for screening tests. Furthermore, genetic testing may confirm the diagnosis in those with limited symptoms who otherwise would have been labeled \"possible HHT\" (see below).<ref name=Guideline/>\n+\n+Genetic diagnosis in HHT is difficult, as mutations occur in numerous different locations in the linked genes, without particular mutations being highly frequent (as opposed to, for instance, the [[ΔF508]] mutation in [[cystic fibrosis]]). [[Sequence analysis]] of the involved genes is therefore the most useful approach (sensitivity 75%), followed by additional testing to detect large deletions and duplications (additional 10%). Not all mutations in these genes have been linked with disease.<ref name=Guideline/>\n+\n+Mutations in the ''MADH4'' gene is usually associated with juvenile polyposis, and detection of such a mutation would indicate a need to screen the patient and affected relatives for polyps and tumors of the large intestine.<ref name=Guideline/>\n+\n+===Критерии===\n+The diagnosis can be made depending on the presence of four criteria, known as the \"[[Curaçao]] criteria\".<ref name=Shovlin2000>{{cite journal |author=Shovlin CL, Guttmacher AE, Buscarini E, ''et al.'' |title=Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber syndrome) |journal=American Journal of Medical Genetics |volume=91 |issue=1 |pages=66–7 |date=Mar 2000 |pmid=10751092 |doi=10.1002/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P}}</ref> If three or four are met, a patient has \"definite HHT\", while two gives \"possible HHT\":\n+# Spontaneous recurrent [[epistaxis]]\n+# Multiple telangiectasias in typical locations (see above)\n+# Proven visceral AVM (lung, liver, brain, spine)\n+# First-degree family member with 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Спонтанное рецидивирующее носовое кровотечение\r\n* Многочисленные телеангиэктазии в типичных местах (см выше)\r\n* Наличие AVM во внутренних органах (легких, печени, головного мозга, позвоночника)\r\n* Член семьи первой степени с 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