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OI
MCID: ORT004
MIFTS: 64

Orthostatic Intolerance (OI)

Categories: Cardiovascular diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Orthostatic Intolerance

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MalaCards integrated aliases for Orthostatic Intolerance:

Name: Orthostatic Intolerance 57 75 73 12 16
Mitral Valve Prolapse 11 75 28 53 5 41 43 14 63 33
Neurocirculatory Asthenia 57 11 28 5 43 14 71
Mitral Valve Prolapse Syndrome 57 71
Systolic Click-Murmur Syndrome 11 33
Irritable Heart 57 71
Familial Orthostatic Tachycardia Due to Norepinephrine Transporter Deficiency 58
Postural Orthostatic Tachycardia Syndrome Due to Net Deficiency 58
Cardiovascular Malfunction Arising from Mental Factors 11
Orthostatic Intolerance Due to Net Deficiency 58
Mitral Valve Prolapse, Familial, X-Linked 71
Prolapsing Mitral Valve Leaflet Syndrome 33
Ballooning Posterior Leaflet Syndrome 33
Mitral Valve Prolapse-Click Syndrome 33
Posterior Mitral Leaflet Deformity 33
Myxomatous Mitral Valve Prolapse 11
Billowing Mitral Valve Leaflet 33
Floppy Mitral Valve Syndrome 33
Pots Due to Net Deficiency 58
Intolerance, Orthostatic 38
Mitral Valvular Prolapse 33
Cardiovascular Neurosis 11
Mitral Leaflet Syndrome 11
Ballooning Mitral Valve 33
Myxomatous Mitral Valve 33
Systolic Click Syndrome 33
Flail Mitral Leaflet 33
Floppy Mitral Valve 11
Da Costa's Syndrome 11
Krishaber's Disease 11
Blue Valve Syndrome 33
Barlow's Syndrome 11
Barlow Syndrome 33
Soldiers Heart 57
Oi 73

Characteristics:


Inheritance:

Orthostatic Intolerance: Autosomal dominant 57
Postural Orthostatic Tachycardia Syndrome Due to Net Deficiency: Autosomal dominant 58

Prevelance:

Postural Orthostatic Tachycardia Syndrome Due to Net Deficiency: <1/1000000 (Worldwide) 58

Age Of Onset:

Postural Orthostatic Tachycardia Syndrome Due to Net Deficiency: Adult 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
based on a report of a family


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Cardiovascular diseases Neuronal diseases Mental diseases
See all MalaCards categories (disease lists)
ICD10: 32
ICD11: 33
Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 11 DOID:11569 DOID:988
OMIM® 57 604715
ICD9CM 34 306.2
NCIt 49 C50655
SNOMED-CT 68 46219009 8074002
ICD10 via Orphanet 32 I95.1
Orphanet 58 ORPHA443236
UMLS 71 C0026267 C0027821 C2930833 more
Sources

Summaries for Orthostatic Intolerance

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MedlinePlus: 41 What is the mitral valve? The mitral valve is one of the four valves in your heart. Heart valves have flaps that open and close. The flaps make sure that blood flows in the right direction through your heart and to the rest of your body. When your heart beats, the flaps open to let blood through. Between heartbeats they close to stop the blood from flowing backwards. The mitral valve opens to let blood flow from your heart's upper left chamber to the lower left chamber. When the lower left chamber contracts (squeezes) to pump blood to your body, the mitral valve closes tightly to keep any blood from flowing backwards. What is mitral valve prolapse (MVP)? Mitral valve prolapse (MVP) happens when the flaps of the mitral valve become floppy and don't close tightly. In some cases, blood may leak backwards through the valve to the chamber it came from. This is called backflow, or regurgitation. When there is a lot of mitral valve backflow, the heart can't push enough blood out to the body. But most people who have MVP don't have any backflow. In fact, MVP doesn't cause any health problems for most people who have it. Who is more likely to develop mitral valve prolapse (MVP)? Anyone can have MVP. Most people who have it were born with it. MVP tends to run in families, but researchers don't know the exact cause. You may be more likely to develop MVP if you: Are older. The risk of MVP increases as aging affects the valve. Had rheumatic fever, a disease that can develop after a strep throat infection and cause damage to the heart valves. Were born with a connective tissue disorder, such as Marfan syndrome or Ehlers-Danlos syndrome. Have Graves' disease, a type of thyroid condition. Have scoliosis (a side-to-side curve of the spine) or other problems with the bones of your body. Have some types of muscular dystrophy. Mitral valve prolapse with backflow is most common in men and people who have high blood pressure. What are the symptoms of mitral valve prolapse (MVP)? Most people who have MVP don't have any symptoms. But if it does cause symptoms, they may include: Heart palpitations (feeling that your heart is fluttering, skipping beats, or beating too hard or too fast) Shortness of breath (feeling like you can't get enough air) A cough Fatigue, dizziness, or anxiety A migraine Chest pain What other problems can mitral valve prolapse (MVP) cause? In rare cases, MVP can cause other problems. They're most often caused by backflow. They can include: Arrhythmia, a problem with the rate or rhythm of your heartbeat Endocarditis, an infection in the lining of the heart and heart valves Heart failure How is mitral valve prolapse (MVP) diagnosed? Health care providers often find MVP during routine health check-ups. If you have MVP, your provider may hear a clicking sound when listening to your heart with a stethoscope. If blood flows backwards through the valve, your heart may also make a whooshing sound called a heart murmur. You may also need certain heart tests. The most useful test is an echocardiogram, or echo. This is a type of ultrasound that uses sound waves to make a moving picture of your heart. What are the treatments for mitral valve prolapse (MVP)? Most people don't need any treatment for MVP. If you have symptoms with little or no backflow, you may only need medicine to relieve your discomfort. If the amount of backflow is significant, you may need treatment to prevent other heart problems from developing. Treatments may include: Medicines to help your heart work better. Heart surgery to repair or replace a very abnormal mitral valve with backflow. The goal of surgery is to improve your symptoms and reduce your risk of developing heart failure. When possible, valve repair is generally preferred over replacement. That's because repairs are less likely to weaken the heart muscle, and they're less likely to cause heart infection. Can mitral valve prolapse be prevented? You can't prevent mitral valve prolapse. But if you have mitral valve prolapse, you can help prevent the rare but serious problems it can cause by: Brushing and flossing your teeth regularly. That helps keep bacteria out of your bloodstream, which further reduces the rare risk of a heart infection. Asking your provider if you need to take antibiotics before dental work or surgery to lower your risk of heart infection. This mostly applies to people who have had valve repair or replacement surgery. Getting regular check-ups and taking any medicines that your provider may have prescribed. Making heart-healthy habits part of your life to prevent heart disease. NIH: National Heart, Lung, and Blood Institute

MalaCards based summary: Orthostatic Intolerance, also known as mitral valve prolapse, is related to postural orthostatic tachycardia syndrome and mitral valve prolapse 1, and has symptoms including angina pectoris, chest pain and edema. An important gene associated with Orthostatic Intolerance is SLC6A2 (Solute Carrier Family 6 Member 2), and among its related pathways/superpathways are Extracellular matrix organization and ACE Inhibitor Pathway, Pharmacodynamics. The drugs Prednisolone phosphate and Prednisolone acetate have been mentioned in the context of this disorder. Affiliated tissues include heart, thyroid and lung, and related phenotypes are elevated urinary norepinephrine and orthostatic tachycardia

PubMed Health : 63 Mitral valve prolapse: Mitral (MI-tral) valve prolapse (MVP) is a condition in which the heart's mitral valve doesn't work well. The flaps of the valve are "floppy" and don't close tightly. These flaps normally help seal or open the valve. Much of the time, MVP doesn't cause any problems. Rarely, blood can leak the wrong way through the floppy valve. This can lead to palpitations, shortness of breath, chest pain, and other symptoms. (Palpitations are feelings that your heart is skipping a beat, fluttering, or beating too hard or too fast.)

Orphanet: 58 A rare, genetic, primary orthostatic disorder characterized by dizziness, palpitations, fatigue, blurred vision and tachycardia following postural change from a supine to an upright position, in the absence of hypotension. A syncope with transient cognitive impairment and dyspnea may also occur. The norepinephrine transporter deficiency leads to abnormal uptake and high plasma concentrations of norepinephrine.

Disease Ontology 11 Neurocirculatory asthenia: A somatoform disorder that involves heart disease symptoms without any identifiable physiological abnormatlities.

Mitral valve prolapse: A mitral valve disease where one or both of the cusps of the mitral valve bulge or collapse backward in the left atrium during systole.

UniProtKB/Swiss-Prot: 73 Syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high.

Wikipedia 75 Orthostatic intolerance: Orthostatic intolerance (OI) is the development of symptoms when standing upright that are relieved when... more...

Mitral valve prolapse: Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an... more...

More information from OMIM: 604715
Sources

Related Diseases for Orthostatic Intolerance

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Diseases related to Orthostatic Intolerance via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 566)
# Related Disease Score Top Affiliating Genes
1 postural orthostatic tachycardia syndrome 33.0 SLC6A2 REN FBN2 FBN1 COL5A1 AGTR1
2 mitral valve prolapse 1 33.0 MMVP1 DCHS1
3 syncope 32.0 SLC6A2 DBH
4 pure autonomic failure 31.9 REN DBH
5 mitral valve insufficiency 31.7 TTN REN FBN1 ELN
6 aortic valve insufficiency 31.6 REN FBN2 FBN1 ELN
7 tricuspid valve prolapse 31.5 PLOD1 FLNA FBN2 FBN1 COL5A1
8 pneumothorax 31.4 FBN1 ELN COL5A1
9 hypermobile ehlers-danlos syndrome 31.3 PLOD1 FBN1 COL5A1
10 pulmonary hypertension 31.2 REN NOS3 NOS2 ELN AGTR1
11 heart valve disease 31.1 TTN REN FBN1 ELN
12 stroke, ischemic 31.1 REN NOS3 FBN1 AGTR1
13 pulmonary edema 31.1 REN NOS3 NOS2 AGTR1
14 scoliosis 31.0 TTN-AS1 TTN PLOD1 FBN2 FBN1 ELN
15 patent ductus arteriosus 1 31.0 TTN REN FLNA FBN1 ELN
16 migraine with aura 31.0 NOS3 FLNA DBH
17 heart disease 31.0 TTN REN NOS3 NOS2 FLNA FBN1
18 ehlers-danlos syndrome 31.0 TTN PLOD1 FLNA FBN2 FBN1 ELN
19 idiopathic scoliosis 31.0 NOS2 FBN1 ELN
20 collagen disease 30.9 PLOD1 FBN1 ELN COL5A1
21 stickler syndrome, type i 30.9 FLNA FBN2 FBN1 COL5A1
22 hypertensive heart disease 30.9 TTN REN AGTR1
23 hypertension, essential 30.9 SLC6A2 REN NOS3 NOS2 FBN1 ELN
24 stickler syndrome 30.9 FBN2 FBN1 ELN COL5A1
25 lipoprotein quantitative trait locus 30.9 TTN REN NOS3 NOS2 FBN1 ELN
26 hypermobility syndrome 30.8 PLOD1 FBN1 COL5A1
27 contractural arachnodactyly, congenital 30.8 FBN2 FBN1 ELN
28 third-degree atrioventricular block 30.8 TTN-AS1 TTN REN
29 aortic valve disease 2 30.7 TTN REN PDLIM1 FBN1 ELN
30 brittle bone disorder 30.7 PLOD1 FBN2 FBN1 ELN COL5A1
31 congestive heart failure 30.7 TTN REN DBH AGTR1
32 fibromuscular dysplasia 30.7 REN COL5A1 AGTR1
33 atrial heart septal defect 30.7 TTN REN FLNA FBN1 ELN
34 stiff skin syndrome 30.7 FBN2 FBN1 ELN
35 aortic aneurysm, familial thoracic 1 30.7 REN PLOD1 NOS3 FLNA FBN2 FBN1
36 vascular disease 30.7 NOS3 NOS2 FBN1 ELN AGTR1
37 aortic dissection 30.7 NOS3 FBN1 ELN COL5A1
38 aortic aneurysm 30.7 REN NOS3 FBN2 FBN1 ELN AGTR1
39 glaucoma, primary open angle 30.7 NOS3 FBN1 ELN COL5A1
40 weill-marchesani syndrome 30.7 FBN2 FBN1 ELN
41 inguinal hernia 30.7 FBN1 ELN COL5A1
42 portal hypertension 30.7 REN NOS3 ELN AGTR1
43 aortic aneurysm, familial thoracic 4 30.7 PLOD1 FLNA FBN2 FBN1 COL5A1
44 hypertrophic cardiomyopathy 30.7 TTN-AS1 TTN REN NOS3 FBN1 ELN
45 aortic disease 30.6 REN FBN1 ELN
46 mitral valve disease 30.6 TTN REN FLNA FBN2 FBN1 ELN
47 dilated cardiomyopathy 30.6 TTN-AS1 TTN REN NOS3 FBN1 ELN
48 aortic valve disease 1 30.6 REN NOS3 FLNA FBN2 FBN1 ELN
49 pulmonary valve insufficiency 30.6 REN FBN1
50 tetralogy of fallot 30.6 TTN REN FLNA FBN1 ELN DBH

Graphical network of the top 20 diseases related to Orthostatic Intolerance:



Diseases related to Orthostatic Intolerance
Sources

Symptoms & Phenotypes for Orthostatic Intolerance

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Human phenotypes related to Orthostatic Intolerance:

30
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 elevated urinary norepinephrine 30 Very rare (1%) HP:0003345
2 orthostatic tachycardia 30 Very rare (1%) HP:0012173

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Cardiovascular Heart:
mitral valve prolapse
syncope
orthostatic tachycardia
exertional tachycardia

Cardiovascular Vascular:
hypertension, variable
orthostatic intolerance

Respiratory Lung:
dyspnea

Clinical features from OMIM®:

604715 (Updated 08-Dec-2022)

UMLS symptoms related to Orthostatic Intolerance:


angina pectoris; chest pain; edema

MGI Mouse Phenotypes related to Orthostatic Intolerance:

45 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.3 AGTR1 DBH ELN FBN1 FBN2 FLNA
2 nervous system MP:0003631 10.29 AGTR1 DBH DCHS1 FBN1 FBN2 FLNA
3 growth/size/body region MP:0005378 10.28 AGTR1 COL5A1 DBH DCHS1 FBN1 FBN2
4 cardiovascular system MP:0005385 10.24 AGTR1 COL5A1 DBH DCHS1 ELN FBN1
5 behavior/neurological MP:0005386 10.17 AGTR1 DBH FBN1 FBN2 FLNA NOS2
6 renal/urinary system MP:0005367 10.15 AGTR1 DCHS1 FBN1 FBN2 NOS2 NOS3
7 muscle MP:0005369 10.13 ELN FBN1 FBN2 NOS2 NOS3 PLOD1
8 craniofacial MP:0005382 9.95 FBN1 FBN2 FLNA NOS2 RPS6KA3 TRPS1
9 respiratory system MP:0005388 9.91 DCHS1 ELN FBN1 FBN2 FLNA NOS2
10 skeleton MP:0005390 9.9 DBH DCHS1 ELN FBN1 FBN2 FLNA
11 mortality/aging MP:0010768 9.86 AGTR1 COL5A1 DBH DCHS1 ELN FBN1
12 integument MP:0010771 9.28 COL5A1 DBH FBN1 FBN2 NOS2 PLOD1
Sources

Drugs & Therapeutics for Orthostatic Intolerance

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PubMed Health treatment related to Orthostatic Intolerance: 63

Most people who have mitral valve prolapse (MVP) don't need treatment because they don't have symptoms and complications. Even people who do have symptoms may not need treatment . The presence of symptoms doesn't always mean that the backflow of blood through the valve is significant. People who have MVP and troublesome mitral valve backflow usually need treatment . MVP is treated with medicines, surgery , or both. The goals of treating MVP include: Preventing infective endocarditis (IE), arrhythmias , and other complications Relieving symptoms Correcting the underlying mitral valve problem, if necessary

Drugs for Orthostatic Intolerance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 153)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Prednisolone phosphate Approved, Vet_approved Phase 2, Phase 3 302-25-0
2
Prednisolone acetate Approved, Vet_approved Phase 2, Phase 3 52-21-1
3
Prednisolone Approved, Vet_approved Phase 2, Phase 3 50-24-8 4894 5755
4
Methylprednisolone hemisuccinate Approved Phase 2, Phase 3 2921-57-5 1875
5
Methylprednisolone Approved, Vet_approved Phase 2, Phase 3 83-43-2 4159 6741
6
Carbidopa Approved Phase 2, Phase 3 28860-95-9 34359 38101
7
Flecainide Approved, Withdrawn Phase 3 54143-55-4 3356
8
Metoprolol Approved, Investigational Phase 3 37350-58-6, 51384-51-1 4171
9
Dopamine Approved Phase 2, Phase 3 62-31-7, 51-61-6 681
10
Droxidopa Approved, Investigational Phase 2, Phase 3 23651-95-8 443940 92974
11
Prednisolone hemisuccinate Experimental Phase 2, Phase 3 2920-86-7 4897
12 Neuroprotective Agents Phase 2, Phase 3
13 Hormone Antagonists Phase 2, Phase 3
14 Antiemetics Phase 2, Phase 3
15 glucocorticoids Phase 2, Phase 3
16
Methylprednisolone Acetate Phase 2, Phase 3 584547
17 Dopamine Agents Phase 2, Phase 3
18 Aromatic Amino Acid Decarboxylase Inhibitors Phase 2, Phase 3
19 Sodium Channel Blockers Phase 3
20 Diuretics, Potassium Sparing Phase 3
21 Antihypertensive Agents Phase 2, Phase 3
22 Antiparkinson Agents Phase 2, Phase 3
23
Estradiol Approved, Investigational, Vet_approved Phase 2 50-28-2 5757
24
Polyestradiol phosphate Approved Phase 2 28014-46-2
25
Ganirelix Approved Phase 2 124904-93-4 44208957 16186319 16130966
26
Progesterone Approved, Vet_approved Phase 2 57-83-0 5994
27
Atomoxetine Approved Phase 1, Phase 2 82248-59-7, 83015-26-3 54841
28
Propranolol Approved, Investigational Phase 1, Phase 2 318-98-9, 525-66-6 62882 4946
29
Entacapone Approved, Investigational Phase 1, Phase 2 130929-57-6 5281081
30
Isosorbide dinitrate Approved, Investigational Phase 1, Phase 2 87-33-2 3780 6883
31
Isosorbide Approved, Investigational Phase 1, Phase 2 652-67-5 99937 12597
32
Memantine Approved, Investigational Phase 1, Phase 2 41100-52-1, 19982-08-2 4054
33
Indomethacin Approved, Investigational Phase 1, Phase 2 53-86-1 3715
34
Acetazolamide Approved, Vet_approved Phase 1, Phase 2 59-66-5, 1424-27-7 1986
35
Nitric Oxide Approved Phase 1, Phase 2 10102-43-9 145068
36
Sertraline Approved Phase 1, Phase 2 79617-96-2 68617
37
Octreotide Approved, Investigational Phase 1, Phase 2 83150-76-9 383414 6400441
38
Modafinil Approved, Investigational Phase 1, Phase 2 68693-11-8 4236
39
Clonidine Approved Phase 1, Phase 2 4205-91-8, 4205-90-7 2803 20179
40
Mecamylamine Approved, Investigational Phase 1, Phase 2 60-40-2 4032
41
Atenolol Approved Phase 1, Phase 2 29122-68-7 2249
42
Melatonin Approved, Nutraceutical, Vet_approved Phase 1, Phase 2 73-31-4 896
43
1,2-Dihydroxybenzene Experimental Phase 1, Phase 2 120-80-9 289
44 Hormones Phase 2
45 Estrogens Phase 2
46 Estradiol 3-benzoate Phase 2
47 Estradiol 17 beta-cypionate Phase 2
48 Contraceptive Agents Phase 2
49 Progestins Phase 2
50 Vasodilator Agents Phase 1, Phase 2

Interventional clinical trials:

(show top 50) (show all 69)
# Name Status NCT ID Phase Drugs
1 An Adaptive Enrichment Designed, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of Anshen Buxin Liuwei Pills in the Treatment of Cardiac Neurosis Recruiting NCT04932395 Phase 4 Anshen Buxin Liuwei Pill;Placebo
2 Effect of Preoperative Intravenous High Dose Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Patients Scheduled for Total Hip-arthroplasty Completed NCT02445898 Phase 2, Phase 3 Methylprednisolone;Isotonic Sodium Chloride
3 Efficacy of Midodrine for the Prevention of Orthostatic Hypotension During Early Mobilization After Fast-track Hip Arthroplasty - a Randomized, Placebo Controlled Trial. Completed NCT01707953 Phase 3 Midodrine;Placebo
4 Kidney Dopamine Effects on Urinary Sodium Excretion in Postural Tachycardia Syndrome Completed NCT00685919 Phase 2, Phase 3 Carbidopa;Placebo
5 An Investigator-Initiated Prospective Randomized Open-Label Blinded-Endpoint Crossover Trial Comparing the Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse Not yet recruiting NCT05631730 Phase 3 Flecainide;Metoprolol
6 Treatment of Hypotensive Patients Having a Unique Pattern of Autonomic Symptoms Terminated NCT00581477 Phase 2, Phase 3 Droxidopa Oral Product
7 Sex Hormones and Orthostatic Tolerance Completed NCT01153581 Phase 2 Ganirelix acetate;17β-Oestradiol;Progesterone
8 Treatment of Orthostatic Intolerance Active, not recruiting NCT00262470 Phase 1, Phase 2 Acetazolamide;Atomoxetine;Clonidine;Entacapone;Entacapone & Propranolol;Atomoxetine & Propranolol;Indomethacin;Mecamylamine;Isosorbide Dinitrate;Midodrine;Modafinil;Octreotide;Propranolol;Modafinil & Propranolol;Sertraline;memantine
9 V-Chordal Adjustable System for Chordal Replacement in Mitral Valve Insufficiency Due to Leaflet Prolapse Terminated NCT01415947 Phase 2
10 A Double-Blinded, Placebo-Controlled Study To Assess Hemodynamic Changes, Orthostatic Tolerance, Out-Patient Fatigue And Quality Of Life In Neuropathic And Non-Neuropathic POTS Patients In Response To Adrenoreceptor Agonist And Antagonist Terminated NCT03070730 Phase 1, Phase 2 Droxidopa;Atenolol;Placebos
11 A Novel Adjustable Neochordae Technique in Mitral Valve Repair Unknown status NCT04299334 Phase 1
12 Clinical Assessment of the St. Jude Medical (SJM) Percutaneous Mitral Valve Repair (PMVr) Device Concept Completed NCT01500148 Phase 1
13 Orthostatic Intolerance After Bariatric Surgery Completed NCT03808740 Phase 1 Atomoxetine;Placebo
14 The Pathophysiology of Orthostatic Hypotension Completed NCT00748059 Phase 1 phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine;clonidine,yohimbine,metoclopramide,alpha-methyldopa
15 Autonomic Nervous System and Chronic Fatigue Syndrome Completed NCT00580619 Phase 1 L-NMMA trimethaphan;methyldopa
16 Reducing Orthostatic Intolerance With Oral Rehydration in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Active, not recruiting NCT02854683 Phase 1 Normal Saline
17 Clinical Efficacy of High-Sodium Diet and External Abdominal Compression in the Treatment of Orthostatic Intolerance in POTS Terminated NCT01771484 Phase 1
18 Exercise Capacity Evaluation in Patients With Non-rheumatic Mitral Valve Prolapse (MVP) Unknown status NCT02499419
19 A Randomized Trial of Mitral Valve Repair With Leaflet Resection Versus Leaflet Preservation on Functional Mitral Stenosis: The Canadian Mitral Research Alliance (CAMRA-1) Trial Unknown status NCT02552771
20 Patient Specific Mitral Valve Modeling for Surgical Planning and Training Unknown status NCT03609931
21 Primary Mitral Regurgitation Reverse Remodeling Unknown status NCT04067635
22 Hemodynamic Monitorization Using Pulse Counter Vigileo-Flotrac Cardiac Output System in Transapical Off-pump Minimally Invasive Mitral Valve Repair Unknown status NCT03506217
23 Baroreceptor Function and Inflammation in Relation to Orthostatic Intolerance During Early Mobilization After Elective Hip Arthroplasty Unknown status NCT01866787
24 Postoperative Incidence of Orthostatic Intolerance and Hypotension in Patients Undergoing Primary Unicompartmental Knee Arthroplasty (UKA) Unknown status NCT04195360
25 Treatment of Orthostatic Intolerance in Patients With Parkinson's Disease Using Midodrine Unknown status NCT02365012 Midodrine
26 Pathophysiologic Hemodynamics After Primary Unilateral Total Hip Arthroplasty Unknown status NCT03759574
27 Genetic Polymorphisms in Idiopathic Mitral Valve Prolapse :A French Prospective Study Using a Genome Wide Analysis Completed NCT00799565
28 Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse Completed NCT02879825
29 Validation Study Comparing the Cardiac Output Pulmonary Arterial Catheter (Swan Ganz) to the FloWaveâ„¢ 1000 Device Completed NCT00665301
30 Endo-aortic Versus Trans-thoracic Clamping in Right Mini-thoracotomy Mitral Valve Repair: Outcome on Myocardial Pro-tection Completed NCT04231903
31 Automated Algorithm Based Analysis of Phonocardiograms of Newborns Completed NCT02105480
32 Safety and Performance Study of the Harpoon Medical Transapical Suturing Device (TSD-5) in Subjects With Degenerative Mitral Regurgitation - EFS/CE Mark Study for the Harpoon Medical Device in Poland Completed NCT02771275
33 Mitral TRans-Apical neoChordal Echo-guided Repair (TRACER) Trial Completed NCT02768870
34 Automatic Differentiation of Innocent and Pathologic Murmurs in Pediatrics Completed NCT02512341
35 Effects of Exercise in Orthostatic Intolerance Completed NCT00770484 Propranolol then Placebo;Placebo then Propranolol
36 Electracupuncture Could Ameliorate Orthostatic Intolerance After Weightlessness by Improving Cardiovascular Function Completed NCT02300207
37 Incidence of Postoperative Orthostatic Intolerance and Postoperative Orthostatic Hypotension in Patients Undergoing Unilateral Total Knee Arthroplasty Completed NCT03743116
38 Mechanisms of Orthostatic Intolerance in Spinal Cord Injured Individuals and Following Bed Rest Completed NCT00175773
39 Clinical Laboratory Evaluation of Chronic Orthostatic Intolerance Completed NCT00069693
40 Assessment of Objective Sleep Disturbances in Orthostatic Intolerance Completed NCT00581022
41 Cardiovagal Baroreflex Deficits Impair Neurovascular Coupling and Cognition in Postural Tachycardia Syndrome Completed NCT03261570 Early Phase 1 Pyridostigmine;Digoxin;Placebo
42 Electroencephalographic (EEG) Characteristics of Postural Tachycardia Syndrome (POTS) and Syncope (Without POTS) During Head-upright Tilt Table Testing Completed NCT02167412
43 Neural and Mechanical Baroreflex Sensitivity and Cerebral Blood Flow Completed NCT01498809 Midodrine
44 Dynamic Evaluation of Myocardial Fibrosis and Structural Determinants of Ventricular Arrhythmia in Mitral Valve Prolapse (STAMP-2 : STretch and Myocardial Characterization in Arrythmogenic Mitral Valve Prolapse-2) Recruiting NCT04852731
45 Genetic and Phenotypic Characteristics of Mitral Valve Prolapse Recruiting NCT03884426
46 Impact of Preoperative Myocardial Fibrosis Related to Mitral Valve Prolapse on Postoperative Left Ventricular Remodeling Recruiting NCT05284058
47 Prognostic Impact of the Location of Mitral Valve Prolapse on the Long-term Results of Mitral Plasty Recruiting NCT03113552
48 Genetic Basis of Mitral Valve Prolapse Recruiting NCT01719211
49 Electrophysiological Substrate in Patients With Barlow's Disease: Clinical Predictors of Arrhythmic Events and Impact of Mitral Surgery Recruiting NCT05562804
50 The AcChord Study: A Multicenter Post-Market Observational Registry of the NeoChord Artificial Chordae Delivery System Recruiting NCT04190602

Search NIH Clinical Center for Orthostatic Intolerance

Cochrane evidence based reviews: neurocirculatory asthenia

Sources

Genetic Tests for Orthostatic Intolerance

About this section

Genetic tests related to Orthostatic Intolerance:

# Genetic test Affiliating Genes
1 Mitral Valve Prolapse 28
2 Neurocirculatory Asthenia 28 SLC6A2
Sources

Anatomical Context for Orthostatic Intolerance

About this section

Organs/tissues related to Orthostatic Intolerance:

MalaCards : Heart, Thyroid, Lung, Spinal Cord, Kidney, Eye, Smooth Muscle
Sources

Publications for Orthostatic Intolerance

About this section

Articles related to Orthostatic Intolerance:

(show top 50) (show all 6902)
# Title Authors PMID Year
1
Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. 53 62 57 5
10684912 2000
2
Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter. 53 62 5
11875370 2002
3
The importance of orthostatic intolerance in the chronic fatigue syndrome. 62 57
10037115 1999
4
Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process. 62 57
7371133 1980
5
Where are the diseases of yesteryear? DaCosta's syndrome, soldiers heart, the effort syndrome, neurocirculatory asthenia--and the mitral valve prolapse syndrome. 62 57
770030 1976
6
THE SYMPATHETIC NERVOUS SYSTEM AND THE "IRRITABLE HEART OF SOLDIERS.". 62 57
20769100 1918
7
SCN5A Variants as Genetic Arrhythmias Triggers for Familial Bileaflet Mitral Valve Prolapse. 62 41
36430924 2022
8
Truncations of titin causing dilated cardiomyopathy. 5
22335739 2012
9
Effects of volume loading and pressor agents in idiopathic orthostatic tachycardia. 57
9244228 1997
10
Mitral Annular Disjunction Assessed Using CMR Imaging: Insights From the UK Biobank Population Study. 41
36280553 2022
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Every day mitral valve reconstruction: What has changed over the last 15 years? 41
36191013 2022
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Slender, older women appear to be more susceptible to nontuberculous mycobacterial lung disease. 53 62
20189150 2010
13
Marfan syndrome and its disorder in periodontal tissues. 53 62
19199346 2009
14
Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan? 53 62
18242274 2008
15
AGT and ACE genes influence classic mitral valve prolapse predisposition in Marfan patients. 53 62
17379330 2008
16
Single nucleotide polymorphisms in the human norepinephrine transporter gene affect expression, trafficking, antidepressant interaction, and protein kinase C regulation. 53 62
15894713 2005
17
Orthostatic intolerance: potential pathophysiology and therapy. 53 62
15612527 2004
18
Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function. 53 62
14726430 2004
19
Fibrillin and other matrix proteins in mitral valve prolapse syndrome. 53 62
14759433 2004
20
Association between fibrillin-1 gene exon 15 and 27 polymorphisms and risk of mitral valve prolapse. 53 62
12918850 2003
21
A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters. 53 62
12805287 2003
22
Autonomic control after blockade of the norepinephrine transporter: a model of orthostatic intolerance. 53 62
12391111 2002
23
The polymorphisms of codon 727 and 52 of thyroid-stimulating hormone receptor gene are not associated with mitral valve prolapse syndrome in Taiwan Chinese. 53 62
12558129 2002
24
Genetic basis of clinical catecholamine disorders. 53 62
12438171 2002
25
Angiotensin II type 1 receptor gene adenine/cytosine1166 polymorphism is not associated with mitral valve prolapse syndrome in Taiwan Chinese. 53 62
11999641 2002
26
Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance. 53 62
11804991 2002
27
Biogenic amine transporters: regulation in flux. 53 62
10851182 2000
28
Angiotensin II type 1 receptor gene polymorphism and mitral valve prolapse syndrome. 53 62
10618569 2000
29
Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome. 53 62
9837823 1998
30
A new and rare form of Williams' syndrome. 53 62
8351994 1993
31
Orthostatic Intolerance and Chiari I Malformation. 62
36424063 2023
32
Malmö POTS symptom score: Assessing symptom burden in postural orthostatic tachycardia syndrome. 62
36111700 2023
33
Effects of short-term hypercaloric nutrition on orthostatic tolerance in healthy individuals: a randomized controlled crossover study. 62
36195683 2022
34
Utricular dysfunction in patients with orthostatic hypotension. 62
36074194 2022
35
Fatigue, post-exertional malaise and orthostatic intolerance: a map of Cochrane evidence relevant to rehabilitation for people with post COVID-19 condition. 62
36472558 2022
36
Sympathetic toggled sinus rate acceleration as a mechanism of sustained sinus tachycardia in chronic orthostatic intolerance syndrome. 62
35995322 2022
37
The role of otolith reflexes in orthostatic intolerance. 62
36255648 2022
38
Preferential impairment of parasympathetic autonomic function in type 2 diabetes. 62
36137485 2022
39
Mitral Annulus Disjunction and Arrhythmic Mitral Valve Prolapse: Emerging Role of Cardiac Magnetic Resonance Imaging in the Workup. 62
36451946 2022
40
An autopsy case of sudden unexpected death of a young adult with progressive intraventricular conduction delay. 62
36401979 2022
41
The leaflet-annulus index in canine myxomatous mitral valve disease. 62
36029573 2022
42
Soldiers' Heart: A Prospective Study of Cardiac Remodeling in Soldiers Undergoing Progressive Intensity Exercise Training. 62
35881923 2022
43
Amlodipine decreases mitral regurgitation volume in dogs over 7 days: A study of 24 dogs with myxomatous mitral valve degeneration. 62
35414938 2022
44
Validation of a focused echocardiographic training program in first opinion practice. 62
36221315 2022
45
Effect of standard-dose and high-dose pimobendan on select indices of renal and cardiac function in dogs with American College of Veterinary Internal Medicine stage B2 myxomatous mitral valve disease. 62
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46
Retrospective evaluation of clinical signs, clinical course, and prognosis between dogs with left atrial rupture secondary to myxomatous mitral valve disease and those with neoplastic cardiac tamponade (2015-2019): 70 cases. 62
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Surgical treatment for left atrial rupture due to myxomatous mitral valve disease in three dogs: A case report. 62
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Isolated hypoaldosteronism managed by DOCP in a dog with chronic kidney disease and hypercortisolism. 62
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Evaluation of urinary neutrophil gelatinase-associated lipocalin to detect renal tubular damage in dogs with stable myxomatous mitral valve disease. 62
36196592 2022
50
Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis. 62
36395340 2022
Sources

Variations for Orthostatic Intolerance

About this section

ClinVar genetic disease variations for Orthostatic Intolerance:

5 (show all 25)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FBN1 NM_000138.5(FBN1):c.6800A>T (p.Asn2267Ile) SNV Pathogenic
 373981 rs1057518812 GRCh37: 15:48722939-48722939
GRCh38: 15:48430742-48430742
2 FBN1 NM_000138.5(FBN1):c.3757_3760del (p.Gln1253fs) DEL Pathogenic
 978559 rs2043485390 GRCh37: 15:48776093-48776096
GRCh38: 15:48483896-48483899
3 FBN1 NM_000138.5(FBN1):c.4388A>G (p.Asn1463Ser) SNV Pathogenic
 523334 rs1555397413 GRCh37: 15:48762902-48762902
GRCh38: 15:48470705-48470705
4 PACS1 NM_018026.4(PACS1):c.607C>T (p.Arg203Trp) SNV Pathogenic
 39581 rs398123009 GRCh37: 11:65978677-65978677
GRCh38: 11:66211206-66211206
5 PLOD1 GRCh37/hg19 1p36.22(chr1:12019879-12028775) CN GAIN Pathogenic
 523241 GRCh37: 1:12019879-12028775
GRCh38:
6 SLC6A2 NM_001172501.3(SLC6A2):c.1369G>C (p.Ala457Pro) SNV Pathogenic
 14006 rs121918126 GRCh37: 16:55731917-55731917
GRCh38: 16:55698005-55698005
7 COL5A1 NM_000093.5(COL5A1):c.608G>T (p.Gly203Val) SNV Likely Pathogenic
 523328 rs1554781700 GRCh37: 9:137593133-137593133
GRCh38: 9:134701287-134701287
8 RPS6KA3 NM_004586.3(RPS6KA3):c.533C>G (p.Ala178Gly) SNV Likely Pathogenic
 374121 rs1057518914 GRCh37: X:20211665-20211665
GRCh38: X:20193547-20193547
9 TTN-AS1, TTN NM_001267550.2(TTN):c.94103_94107del (p.Ile31368fs) DEL Likely Pathogenic
 202493 rs769488730 GRCh37: 2:179412246-179412250
GRCh38: 2:178547519-178547523
10 FBN1 NM_000138.5(FBN1):c.7829A>G (p.Glu2610Gly) SNV Likely Pathogenic
 523335 rs1555393889 GRCh37: 15:48707955-48707955
GRCh38: 15:48415758-48415758
11 TRPS1 NM_014112.5(TRPS1):c.1230G>A (p.Trp410Ter) SNV Likely Pathogenic
 373946 rs1057518791 GRCh37: 8:116616966-116616966
GRCh38: 8:115604739-115604739
12 NSDHL NM_015922.3(NSDHL):c.1054C>G (p.Leu352Val) SNV Uncertain Significance
 373975 rs142351862 GRCh37: X:152037592-152037592
GRCh38: X:152869048-152869048
13 SLC6A2 NM_001172501.3(SLC6A2):c.*1017G>A SNV Uncertain Significance
 319838 rs886052141 GRCh37: 16:55737275-55737275
GRCh38: 16:55703363-55703363
14 FBN1 NM_000138.5(FBN1):c.1900T>C (p.Ser634Pro) SNV Uncertain Significance
 568701 rs1566914005 GRCh37: 15:48797282-48797282
GRCh38: 15:48505085-48505085
15 BMPR2 NM_001204.7(BMPR2):c.2948G>A (p.Arg983Gln) SNV Uncertain Significance
 333652 rs148099152 GRCh37: 2:203424500-203424500
GRCh38: 2:202559777-202559777
16 SLC6A2 NM_001172501.3(SLC6A2):c.*414_*415insC INSERT Uncertain Significance
 319824 rs886052137 GRCh37: 16:55736672-55736673
GRCh38: 16:55702760-55702761
17 SLC6A2 NM_001172501.3(SLC6A2):c.*396_*397dup DUP Uncertain Significance
 319819 rs35571499 GRCh37: 16:55736651-55736652
GRCh38: 16:55702739-55702740
18 SLC6A2 NM_001172501.3(SLC6A2):c.*414_*415dup DUP Uncertain Significance
 319822 rs72297759 GRCh37: 16:55736659-55736660
GRCh38: 16:55702747-55702748
19 SLC6A2 NM_001172501.3(SLC6A2):c.*416del DEL Uncertain Significance
 319825 rs113163898 GRCh37: 16:55736674-55736674
GRCh38: 16:55702762-55702762
20 SLC6A2 NM_001172501.3(SLC6A2):c.*306C>T SNV Uncertain Significance
 319817 rs192171814 GRCh37: 16:55736564-55736564
GRCh38: 16:55702652-55702652
21 SLC6A2 NM_001172501.3(SLC6A2):c.*919_*921del DEL Uncertain Significance
 319834 rs540636734 GRCh37: 16:55737176-55737178
GRCh38: 16:55703264-55703266
22 SLC6A2 NM_001172501.3(SLC6A2):c.*401_*402insCA INSERT Uncertain Significance
 319823 rs201774381 GRCh37: 16:55736659-55736660
GRCh38: 16:55702747-55702748
23 MAP2K2 NM_030662.4(MAP2K2):c.514A>G (p.Lys172Glu) SNV Uncertain Significance
 523536 rs1413580671 GRCh37: 19:4102388-4102388
GRCh38: 19:4102390-4102390
24 SLC39A13 NM_001128225.3(SLC39A13):c.398C>T (p.Thr133Met) SNV Uncertain Significance
 196579 rs140574574 GRCh37: 11:47433573-47433573
GRCh38: 11:47412022-47412022
25 SLC6A2 NM_001172501.3(SLC6A2):c.*415dup DUP Likely Benign
 319821 rs72297759 GRCh37: 16:55736659-55736660
GRCh38: 16:55702747-55702748

UniProtKB/Swiss-Prot genetic disease variations for Orthostatic Intolerance:

73
# Symbol AA change Variation ID SNP ID
1 SLC6A2 p.Ala457Pro VAR_010022 rs121918126

Sources

Expression for Orthostatic Intolerance

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Search GEO for disease gene expression data for Orthostatic Intolerance.
Sources

Pathways for Orthostatic Intolerance

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Pathways related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Extracellular matrix organization 66
Show member pathways
 12 PLOD1 FBN2 FBN1 ELN COL5A1
2
ACE Inhibitor Pathway, Pharmacodynamics 60
Show member pathways
 11.55 REN NOS3 AGTR1
3
Elastic fibre formation 66
Show member pathways
 11.24 FBN2 FBN1 ELN
4
NO-dependent CFTR activation (normal and CF) 22
10.37 NOS3 NOS2
5
Hypothesized pathways in pathogenesis of cardiovascular disease 74
10.32 FLNA FBN2 FBN1 AGTR1
Sources

GO Terms for Orthostatic Intolerance

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Biological processes related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to lipopolysaccharide GO:0032496 9.97 RPS6KA3 REN NOS3 NOS2
2 embryonic eye morphogenesis GO:0048048 9.76 FBN2 FBN1
3 kidney development GO:0001822 9.73 REN FBN1 DCHS1 AGTR1
4 heart morphogenesis GO:0003007 9.72 COL5A1 DCHS1 FLNA
5 arginine catabolic process GO:0006527 9.71 NOS3 NOS2
6 blood vessel remodeling GO:0001974 9.63 NOS3 FLNA DBH
7 cellular biosynthetic process GO:0044249 9.43 NOS3 NOS2
8 sequestering of TGFbeta in extracellular matrix GO:0035583 9.26 FBN2 FBN1
9 renin-angiotensin regulation of aldosterone production GO:0002018 8.92 REN AGTR1

Molecular functions related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 9.86 FBN2 FBN1 ELN COL5A1
2 arginine binding GO:0034618 9.62 NOS3 NOS2
3 tetrahydrobiopterin binding GO:0034617 9.46 NOS3 NOS2
4 nitric-oxide synthase activity GO:0004517 9.26 NOS3 NOS2
5 extracellular matrix constituent conferring elasticity GO:0030023 9.1 FBN2 FBN1 ELN
Sources

Sources for Orthostatic Intolerance

About this section
2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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