PERYTHM
MCID: ERY029
MIFTS: 57

Erythermalgia, Primary (PERYTHM)

Categories: Blood diseases, Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Erythermalgia, Primary

MalaCards integrated aliases for Erythermalgia, Primary:

Name: Erythermalgia, Primary 57 13
Small Fiber Neuropathy 57 43 29 6 70
Primary Erythromelalgia 58 29 6
Primary Erythermalgia 58 72 70
Erythromelalgia, Primary 57 39
Small Nerve Fiber Neuropathy 43
Erythromelalgia, Familial 57
Perythm 72
Sfnp 43
Sfn 43

Characteristics:

Orphanet epidemiological data:

58
primary erythromelalgia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset usually in childhood or adolescence
relief is achieved by cooling or by elevating the extremities
disorder may progress to involve a larger body area
adult-onset is referred to as small fiber neuropathy


HPO:

31
erythermalgia, primary:
Inheritance autosomal dominant inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Erythermalgia, Primary

OMIM® : 57 'Primary erythermalgia' is an autosomal dominant disorder characterized by childhood or adolescent onset of episodic symmetrical red congestion, vasodilatation, and burning pain of the feet and lower legs provoked by exercise, long standing, and exposure to warmth. Relief is obtained with cold (Michiels et al., 2005). The severity of the disorder may progress with age, and symptoms may extend over a larger body area, such as over the ankles and lower legs, and become constant (Mandell et al., 1977). Waxman and Dib-Hajj (2005) provided a review of primary erythermalgia. Although 'primary' or 'familial erythromelalgia' are sometimes used as alternative terms for primary erythermalgia (Waxman and Dib-Hajj, 2005), secondary erythromelalgia is a distinct acquired disorder associated with thrombocythemia or myeloproliferative disorders. It has relatively late onset and symptoms are caused by platelet aggregation in end-arteriolar circulation, leading to ischemia and symptoms (Michiels and van Joost, 1990). Treatment with aspirin, which irreversibly inhibits platelet cyclooxygenase activity, affords relief from acquired erythromelalgia (Michiels et al., 1984; Drenth et al., 1996). Similarly, acquired erythromelalgia vanishes with lowering the platelet count to normal with chemotherapy (Michiels et al., 1985). Van Genderen et al. (1993) emphasized the distinction between hereditary erythermalgia and acquired erythromelalgia. In primary erythermalgia, the burning pain, redness, and warmth of feet and lower legs, with relative sparing of the toes, are easily provoked by warmth and exercise. In contrast, in acquired erythromelalgia the burning pain and red congestion preferentially involves one or more toes or fingers or sole of the forefoot (Michiels and van Joost, 1990). Van Genderen et al. (1993) noted that 3 of the 5 patients reported by Smith and Allen (1938) were not consistent with the diagnosis of primary erythromelalgia because the symptoms were relieved promptly by aspirin, consistent with acquired erythromelalgia. (133020) (Updated 20-May-2021)

MalaCards based summary : Erythermalgia, Primary, also known as small fiber neuropathy, is related to sodium channelopathy-related small fiber neuropathy and sensory peripheral neuropathy, and has symptoms including constipation, myalgia and pruritus. An important gene associated with Erythermalgia, Primary is SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9), and among its related pathways/superpathways are Cardiac conduction and Neuropathic Pain-Signaling in Dorsal Horn Neurons. The drugs Immunoglobulins and Antibodies have been mentioned in the context of this disorder. Affiliated tissues include skin, spinal cord and eye, and related phenotypes are peripheral neuropathy and erythema

MedlinePlus Genetics : 43 Small fiber neuropathy is a condition characterized by severe pain attacks that typically begin in the feet or hands. As a person ages, the pain attacks can affect other regions. Some people initially experience a more generalized, whole-body pain. The attacks usually consist of pain described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy usually begin in adolescence to mid-adulthood.Individuals with small fiber neuropathy cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (allodynia). People affected with this condition may also have a reduced ability to differentiate between hot and cold. However, in some individuals, the pain attacks are provoked by cold or warm triggers.Some affected individuals have urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.

UniProtKB/Swiss-Prot : 72 Primary erythermalgia: Autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands.

Related Diseases for Erythermalgia, Primary

Diseases related to Erythermalgia, Primary via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 208)
# Related Disease Score Top Affiliating Genes
1 sodium channelopathy-related small fiber neuropathy 31.0 SCN9A SCN1A-AS1 SCN11A SCN10A
2 sensory peripheral neuropathy 30.6 SCN9A SCN11A
3 neuropathy 30.6 SCN9A SCN1A-AS1 SCN11A SCN10A
4 peripheral nervous system disease 30.2 SCN9A SCN11A SCN10A
5 autonomic neuropathy 30.1 SCN9A SCN11A
6 generalized epilepsy with febrile seizures plus, type 7 29.7 SCN9A SCN1A-AS1
7 neuropathy, hereditary sensory and autonomic, type iia 29.5 SCN9A SCN1A-AS1
8 charcot-marie-tooth disease 29.4 SCN9A SCN1A-AS1 SCN11A
9 paine syndrome 29.3 SCN9A SCN11A SCN10A
10 causalgia 29.2 SCN9A SCN11A SCN10A
11 episodic pain syndrome, familial, 3 29.2 SCN9A SCN11A SCN10A
12 generalized epilepsy with febrile seizures plus 28.7 SCN9A SCN1A-AS1 SCN11A SCN10A
13 paroxysmal extreme pain disorder 28.7 SCN9A SCN1A-AS1 SCN11A SCN10A
14 erythromelalgia 28.7 SCN9A SCN1A-AS1 SCN11A SCN10A
15 breast cancer 11.3
16 adenoid cystic carcinoma 11.1
17 ductal carcinoma in situ 11.0
18 popliteal pterygium syndrome 10.9
19 fetal encasement syndrome 10.9
20 benign breast adenomyoepithelioma 10.9
21 vulva squamous cell carcinoma 10.9
22 colloid carcinoma of the pancreas 10.9
23 limbal stem cell deficiency 10.9
24 polyneuropathy 10.7
25 autonomic dysfunction 10.6
26 fibromyalgia 10.6
27 sarcoidosis 1 10.5
28 dysautonomia 10.5
29 diabetic neuropathy 10.4
30 fabry disease 10.4
31 paresthesia 10.3
32 complex regional pain syndrome 10.3
33 diabetic polyneuropathy 10.2
34 amyloidosis 10.2
35 autoimmune disease 10.2
36 sjogren syndrome 10.2
37 orthostatic intolerance 10.2
38 postural orthostatic tachycardia syndrome 10.2
39 lyme disease 10.2
40 ehlers-danlos syndrome 10.2
41 alcohol use disorder 10.2
42 encephalopathy 10.1
43 lung cancer susceptibility 3 10.1
44 charcot-marie-tooth disease, demyelinating, type 1a 10.1
45 celiac disease 1 10.1
46 wilson disease 10.1
47 reflex sympathetic dystrophy 10.1
48 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.1
49 leukemia, acute lymphoblastic 10.1
50 vitamin b12 deficiency 10.1

Graphical network of the top 20 diseases related to Erythermalgia, Primary:



Diseases related to Erythermalgia, Primary

Symptoms & Phenotypes for Erythermalgia, Primary

Human phenotypes related to Erythermalgia, Primary:

58 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
2 erythema 58 31 hallmark (90%) Very frequent (99-80%) HP:0010783
3 pruritus 58 31 frequent (33%) Frequent (79-30%) HP:0000989
4 hypothermia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002045
5 recurrent respiratory infections 58 31 occasional (7.5%) Occasional (29-5%) HP:0002205
6 leukemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001909
7 vasculitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002633
8 abnormal autonomic nervous system physiology 31 occasional (7.5%) HP:0012332
9 abnormal thrombocyte morphology 31 occasional (7.5%) HP:0001872
10 hyperhidrosis 31 HP:0000975
11 constipation 31 HP:0002019
12 myalgia 31 HP:0003326
13 abnormality of thrombocytes 58 Occasional (29-5%)
14 abnormality of the nervous system 31 HP:0000707
15 keratoconjunctivitis sicca 31 HP:0001097
16 abnormality of the musculature 31 HP:0003011
17 diarrhea 31 HP:0002014
18 xerostomia 31 HP:0000217
19 blurred vision 31 HP:0000622
20 palpitations 31 HP:0001962
21 jaw pain 31 HP:0040264
22 erythromelalgia 31 HP:0032147

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skin Nails Hair Skin:
hyperhidrosis
reddish or purplish skin discoloration, episodic, associated with pain
decreased intraepithelial nerve fiber density

Head And Neck Eyes:
blurred vision
dry eyes

Head And Neck Face:
jaw pain

Neurologic Peripheral Nervous System:
itching
burning pain, episodic, typically in the distal extremities, particularly the hands and feet (bilateral, symmetric), triggered by warm stimuli, exercise, standing
impaired distal temperature sensation
hypoesthesia over affected areas
autonomic dysfunction (in some patients)

Abdomen Gastrointestinal:
constipation
diarrhea

Cardiovascular Heart:
palpitations

Muscle Soft Tissue:
muscle pain
swelling of the affected areas
myalgias

Head And Neck Mouth:
dry mouth

Clinical features from OMIM®:

133020 (Updated 20-May-2021)

UMLS symptoms related to Erythermalgia, Primary:


constipation; myalgia; pruritus; diarrhea; jaw pain; neuralgia; dryness of eye

Drugs & Therapeutics for Erythermalgia, Primary

Drugs for Erythermalgia, Primary (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 59)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunoglobulins Phase 4
2 Antibodies Phase 4
3 Antibodies, Blocking Phase 4
4
Lacosamide Approved Phase 3 860352-01-8, 175481-36-4 219078
5 Anticonvulsants Phase 3
6 Sodium Channel Blockers Phase 3
7 Diuretics, Potassium Sparing Phase 3
8
Pregabalin Approved, Investigational Phase 2 148553-50-8 5486971
9
Nicotinamide Approved, Investigational Phase 2 98-92-0 936
10
Glutamic acid Approved, Nutraceutical Phase 2 56-86-0 33032
11
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
12
Niacin Approved, Investigational, Nutraceutical Phase 2 59-67-6 938
13 Excitatory Amino Acid Antagonists Phase 2
14 Neurotransmitter Agents Phase 2
15 Psychotropic Drugs Phase 2
16 Hormones Phase 2
17 Anti-Anxiety Agents Phase 2
18 calcium channel blockers Phase 2
19 Calcium, Dietary Phase 2
20 Analgesics Phase 2
21 Pharmaceutical Solutions Phase 2
22 Autoantibodies Phase 2
23 Antimetabolites Phase 2
24 Micronutrients Phase 2
25 Trace Elements Phase 2
26 Vasodilator Agents Phase 2
27 Vitamin B9 Phase 2
28 Nutrients Phase 2
29 Vitamin B Complex Phase 2
30 Hypolipidemic Agents Phase 2
31 Vitamin B3 Phase 2
32 Folate Phase 2
33 Vitamins Phase 2
34 Nicotinic Acids Phase 2
35 Lipid Regulating Agents Phase 2
36 Immunologic Factors Phase 2
37 Rho(D) Immune Globulin Phase 2
38 Immunoglobulins, Intravenous Phase 2
39 gamma-Globulins Phase 2
40
Calcium Nutraceutical Phase 2 7440-70-2 271
41
Hydrocortisone Approved, Vet_approved Phase 1 50-23-7 5754
42
Hydrocortisone acetate Approved, Vet_approved Phase 1 50-03-3
43 Hydrocortisone 17-butyrate 21-propionate Phase 1
44 Hydrocortisone hemisuccinate Phase 1
45
Hydrogen peroxide Approved, Vet_approved 7722-84-1 784
46
Acetylcholine Approved, Investigational 51-84-3 187
47
Ethanol Approved 64-17-5 702
48
Lidocaine Approved, Vet_approved 137-58-6 3676
49
Prilocaine Approved 721-50-6 4906
50
Capsaicin Approved 404-86-4 1548943

Interventional clinical trials:

(show all 34)
# Name Status NCT ID Phase Drugs
1 Anti-CGRP Neutralizing Antibody for Modulation of Neurogenic Inflammation in Trigeminal and Glossopharyngeal Pain Associated With Small Fiber Neuropathy/Fibromyalgia Recruiting NCT04158752 Phase 4 Galcanezumab
2 Efficacy, Safety and Tolerability of Lacosamide in Patients With Gain-of-function Nav1.7 Mutations Related Small Fiber Neuropathy: a Randomized, Double-blind, Placebo Controlled, Crossover Trial Completed NCT01911975 Phase 3 Lacosamide;Placebo
3 Randomized Crossover Trial of Fycompa in the Treatment of Pain Associated With Small Fiber Neuropathy (SFN) Unknown status NCT02511873 Phase 2 Fycompa;Placebo
4 Intravenous Immunoglobulin Therapy for Small Fiber Neuropathy: a Randomized, Double-blind, Placebo-controlled Study on Efficacy and Safety. Completed NCT02637700 Phase 2 Intravenous Immunoglobulin;Placebo
5 Efficacy and Safety of Pregabalin in Treatment of Neuropathic Pain in Patients With Idiopathic Small Fiber Neuropathy Completed NCT02607254 Phase 2 Pregabalin;Placebo
6 A Phase 2, Randomized, Double-blind, Placebo-controlled, 6-Week, Parallel-design Study of the Efficacy and Safety of VX-150 in Treating Subjects With Pain Caused by Small Fiber Neuropathy Completed NCT03304522 Phase 2 VX-150;Placebo
7 Phase 2a, Double-blind, Placebo-controlled, 2-period, Crossover Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Oral Doses of XPF-001 in Patients With Inherited Erythromelalgia. Completed NCT01090622 Phase 1, Phase 2 XPF-001;Placebo
8 Phase 2a, Exploratory, Double-blind, Placebo-controlled Two-part Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of Topically Applied XPF-002 (XEN402 8% w/w Ointment) in Patients With Primary/Inherited Erythromelalgia Completed NCT01486446 Phase 1, Phase 2 XPF-002;Placebo
9 A Double-Blind, Placebo Controlled Trial of Intravenous Immunoglobulin Therapy in Patient With Small Fiber Neuropathy Associated With Autoantibodies to TS-HDS and FGFR3 Recruiting NCT03401073 Phase 2 Intravenous immunoglobulin;0.9% Sodium Chloride
10 A Phase 2 Placebo-Controlled, Double-Blind, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy and Safety of BIIB074 (Vixotrigine) in Treating Pain Experienced by Subjects With Confirmed Small Fiber Neuropathy That is Idiopathic or Associated With Diabetes Mellitus Recruiting NCT03339336 Phase 2 BIIB074;Placebo
11 Evaluation of Nicotinamide Riboside in Prevention of Small Fiber Axon Degeneration and Promotion of Nerve Regeneration Recruiting NCT03912220 Phase 2 Nicotinamide riboside;Placebo Oral Tablet
12 Intravenous Immunoglobulin (IVIG) in the Treatment of Autoimmune Small Fiber Neuropathy Due to TS-HDS and FGFR-3 Antibodies: a Double Blinded Placebo-controlled Phase II Trial Suspended NCT04153422 Phase 2 Gammagard IVIG;Placebo
13 XanaHES: A Phase I, Single Blinded, Central Reader Blinded, Placebo-Controlled, Dose Escalation Study of Xanamem™ to Assess Safety and Tolerability in Healthy Elderly Subjects Completed NCT03830762 Phase 1 Xanamem;Matching Placebo
14 A Randomized, Placebo-Controlled, Optimized Titration Study of ABX-1431 in Adult Patients With Peripheral Neuropathic Pain Completed NCT03447756 Phase 1 ABX-1431;Placebo oral capsule
15 A Double-Blind, Placebo-Controlled, Enriched-Enrollment, Randomized Withdrawal Study to Evaluate an Optimal Methodology for Conducting Proof of Concept Trials in Patients With Chronic Neuropathic Pain Syndromes Using Pregabalin as a Test Drug Completed NCT00570310 Phase 1 Comparator: pregabalin;Comparator: Placebo (unspecified)
16 Nutritional Supplementation With Agmatine Sulfate During Small Fiber Neuropathy Unknown status NCT01524666
17 Small-fiber Neuropathy in Chronic Kidney Disease Unknown status NCT01078857
18 Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan Unknown status NCT02985710
19 A Pilot Study of Small Fiber Neuropathy Prevalence in Fibromyalgia Patients Compared to Healthy Subjects Using Sudoscan® Unknown status NCT03347669
20 Investigation of Sudoscan in the Evaluation of Small Fiber Dysfunction in Korean Patients With Autoimmune Disorders Completed NCT02434458
21 Is Diabetic Peripheral Neuropathy Accompanied by Internal Nerve Damage? A Comparative, Clinical Experimental Study of Peripheral and Visceral Nerve Damage in Diabetic Patients and Healthy Controls Completed NCT01160887
22 Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study Completed NCT02537951
23 Chronic Cough and Small Fiber Neuropathy Recruiting NCT03787511
24 Prevalence and Characteristics of Fabry Disease (FD) in Patients With Stroke or Small Fiber Neuropathy Recruiting NCT03230149
25 Clinical Study Protocol Dorsal Root Ganglion Stimulation for the Management of Painful Intractable Small Fibre Neuropathy Recruiting NCT02435004
26 Autonomic Neuropathy and Its Pathophysiology in Autoimmune Autonomic Neuropathies, Postural Orthostatic Tachycardia Syndrome and Ehlers Danlos Syndromes: Peripheral Autonomic Small Fiber Neuropathy or Central Autonomic Failure? Recruiting NCT04310644
27 The Medico-economic Impact and Quality of Life of the Small-fiber Neuropathy Associated by Using Validated Scales (SF36, DN4, PROFAD SSI, ESPRI) Recruiting NCT03509064
28 Establishing Normative Values for Thermal Detection and Pain Threshold Established by the Psi Method Recruiting NCT04611048
29 Central Pain Location in SCN9A-associated SFN, an fMRI Pilot Study. Recruiting NCT03889080
30 Application of Skin Biopsy in the Early Diagnosis of Small Fiber Neuropathy in Chinese Patients With Diabetes Recruiting NCT04071535
31 Retrospective Study of Causes Associated With Small Fiber Neuropathies. Not yet recruiting NCT04170205
32 Detection of Small Fiber Neuropathy Using Skin Properties Not yet recruiting NCT04759443
33 Spinal Cord Stimulation in Small Fibre Neuropathy: A Pilot Study Terminated NCT02905396
34 Evaluation of Pregabalin in Idiopathic Small Fiber Neuropathy Terminated NCT00787462 Pregabalin;Placebo

Search NIH Clinical Center for Erythermalgia, Primary

Genetic Tests for Erythermalgia, Primary

Genetic tests related to Erythermalgia, Primary:

# Genetic test Affiliating Genes
1 Primary Erythromelalgia 29 SCN9A
2 Small Fiber Neuropathy 29

Anatomical Context for Erythermalgia, Primary

MalaCards organs/tissues related to Erythermalgia, Primary:

40
Skin, Spinal Cord, Eye, Thyroid, Dorsal Root Ganglion, Breast, Lung

Publications for Erythermalgia, Primary

Articles related to Erythermalgia, Primary:

(show top 50) (show all 731)
# Title Authors PMID Year
1
Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. 61 6 57
21698661 2012
2
COL6A5 variants in familial neuropathic chronic itch. 57 6
28073787 2017
3
Paroxysmal itch caused by gain-of-function Nav1.7 mutation. 6 57
24820863 2014
4
Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. 6 57
22826602 2012
5
Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker. 57 6
22035805 2012
6
Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha subunit Nav1.7. 57 6
16216943 2005
7
Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. 57 6
15958509 2005
8
Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. 6 57
15385606 2004
9
Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. 57 6
14985375 2004
10
Autosomal dominant erythromelalgia. 57 6
1536168 1992
11
Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics. 6
30702961 2019
12
Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Nav 1.7 mutation I234T. 6
28658526 2018
13
Atypical changes in DRG neuron excitability and complex pain phenotype associated with a Nav1.7 mutation that massively hyperpolarizes activation. 6
29379075 2018
14
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
15
Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder. 6
24817410 2014
16
Treatment with carbamazepine and gabapentin of a patient with primary erythermalgia (erythromelalgia) identified to have a mutation in the SCN9A gene, encoding a voltage-gated sodium channel. 6
19549232 2009
17
Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation. 6
19369487 2009
18
A novel Nav1.7 mutation producing carbamazepine-responsive erythromelalgia. 6
19557861 2009
19
Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy. 6
16988069 2006
20
Inherited erythermalgia moves a sodium channel into focus. 6
17101882 2006
21
A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. 6
16702558 2006
22
Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. 6
16392115 2006
23
SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. 6
15955112 2005
24
Erythromelalgia: a hereditary pain syndrome enters the molecular era. 57
15929046 2005
25
The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32. 57
11283792 2001
26
Natural history of erythromelalgia: presentation and outcome in 168 patients. 57
10724194 2000
27
Cutaneous pathology in primary erythermalgia. 57
8721588 1996
28
Erythromelalgia: association with hereditary sensory neuropathy and response to amitriptyline. 57
8451013 1993
29
Hereditary erythermalgia and acquired erythromelalgia. 57
8465864 1993
30
Continuous epidural infusion of bupivacaine and fentanyl for erythromelalgia in an adolescent. 57
1734777 1992
31
Erythromelalgia and thrombocythemia: a causal relation. 57
2405024 1990
32
Erythromelalgia caused by platelet-mediated arteriolar inflammation and thrombosis in thrombocythemia. 57
3977194 1985
33
Histopathology of erythromelalgia in thrombocythaemia. 57
6384014 1984
34
"Burning feet" as the only manifestation of dominantly inherited sensory neuropathy. 57
6575233 1983
35
Erythromelalgia. 57
840540 1977
36
The Genetics of Angiokeratoma Corporis Diffusum (Fabry's Disease) and Its Linkage Relations with the Xg Locus. 57
17948499 1965
37
The familial occurrence of erythromelalgia and nephritis. 57
13882378 1962
38
Differential impact of keratinocytes and fibroblasts on nociceptor degeneration and sensitization in small fiber neuropathy. 61
33196576 2021
39
TS-HDS and FGFR3 Antibodies in Small Fiber Neuropathy and Dysautonomia. 61
33792960 2021
40
When POTS is the tip of the iceberg: Rare cases of dysautonomia as a possible manifestation of another disorder. 61
33459162 2021
41
Pain behavior in SCN9A (Nav1.7) and SCN10A (Nav1.8) mutant rodent models. 61
33775738 2021
42
IVIG and Small Fiber Neuropathy: The Ongoing Search for Evidence. 61
33766998 2021
43
Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes. 61
33295647 2021
44
Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy. 61
33766992 2021
45
Peripheral synucleinopathy in Parkinson disease with LRRK2 G2385R variants. 61
33527742 2021
46
Intraepidermal Nerve Fiber Density as Measured by Skin Punch Biopsy as a Marker for Small Fiber Neuropathy: Application in Patients with Fibromyalgia. 61
33802768 2021
47
Fibromyalgia versus small fiber neuropathy: diverse keratinocyte transcriptome signature. 61
33675632 2021
48
Neuropathic pain features suggestive of small fiber neuropathy in fibromyalgia syndrome: a clinical and ultrasonographic study on female patients. 61
33666162 2021
49
Increased peptidergic fibers as a potential cutaneous marker of pain in diabetic small fiber neuropathy. 61
32833793 2021
50
Autoimmune Small Fiber Neuropathy Associated With Ehlers-Danlos Syndrome Treated With Intravenous Immunoglobulins. 61
33596000 2021

Variations for Erythermalgia, Primary

ClinVar genetic disease variations for Erythermalgia, Primary:

6 (show top 50) (show all 319)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4378T>G (p.Phe1460Val) SNV Pathogenic 6352 rs80356478 GRCh37: 2:167083097-167083097
GRCh38: 2:166226587-166226587
2 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2605C>T (p.Leu869Phe) SNV Pathogenic 6364 rs80356476 GRCh37: 2:167133762-167133762
GRCh38: 2:166277252-166277252
3 SCN9A NM_001365536.1(SCN9A):c.647T>C (p.Phe216Ser) SNV Pathogenic 6365 rs80356469 GRCh37: 2:167160789-167160789
GRCh38: 2:166304279-166304279
4 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1185C>A (p.Asn395Lys) SNV Pathogenic 21343 rs80356471 GRCh37: 2:167145076-167145076
GRCh38: 2:166288566-166288566
5 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2501T>G (p.Leu834Arg) SNV Pathogenic 21345 rs80356473 GRCh37: 2:167134666-167134666
GRCh38: 2:166278156-166278156
6 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2620G>C (p.Ala874Pro) SNV Pathogenic 21346 rs80356477 GRCh37: 2:167133747-167133747
GRCh38: 2:166277237-166277237
7 SCN9A NM_001365536.1(SCN9A):c.406A>G (p.Ile136Val) SNV Pathogenic 21348 rs80356468 GRCh37: 2:167163081-167163081
GRCh38: 2:166306571-166306571
8 SCN9A NM_001365536.1(SCN9A):c.701T>C (p.Ile234Thr) SNV Pathogenic 915877 GRCh37: 2:167159800-167159800
GRCh38: 2:166303290-166303290
9 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2606T>A (p.Leu869His) SNV Pathogenic 6349 rs80356475 GRCh37: 2:167133761-167133761
GRCh38: 2:166277251-166277251
10 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1867G>A (p.Asp623Asn) SNV Pathogenic 30358 rs200398202 GRCh37: 2:167141070-167141070
GRCh38: 2:166284560-166284560
11 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2576T>C (p.Ile859Thr) SNV Pathogenic 6350 rs80356474 GRCh37: 2:167133791-167133791
GRCh38: 2:166277281-166277281
12 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1198G>A (p.Val400Met) SNV Pathogenic 538468 rs1553491169 GRCh37: 2:167145063-167145063
GRCh38: 2:166288553-166288553
13 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2827A>C (p.Met943Leu) SNV Pathogenic 441531 rs12478318 GRCh37: 2:167133540-167133540
GRCh38: 2:166277030-166277030
14 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2248A>G (p.Ile750Val) SNV Pathogenic 157597 rs182650126 GRCh37: 2:167136962-167136962
GRCh38: 2:166280452-166280452
15 SCN9A NM_001365536.1(SCN9A):c.901A>T (p.Lys301Ter) SNV Likely pathogenic 1028064 GRCh37: 2:167159600-167159600
GRCh38: 2:166303090-166303090
16 SCN9A NM_001365536.1(SCN9A):c.721T>A (p.Ser241Thr) SNV Conflicting interpretations of pathogenicity 6351 rs80356470 GRCh37: 2:167159780-167159780
GRCh38: 2:166303270-166303270
17 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2192T>A (p.Ile731Lys) SNV Conflicting interpretations of pathogenicity 30357 rs200945460 GRCh37: 2:167137018-167137018
GRCh38: 2:166280508-166280508
18 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1285C>T (p.Arg429Cys) SNV Conflicting interpretations of pathogenicity 548618 rs763256222 GRCh37: 2:167144976-167144976
GRCh38: 2:166288466-166288466
19 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3767A>G (p.Asn1256Ser) SNV Conflicting interpretations of pathogenicity 130265 rs141268327 GRCh37: 2:167094638-167094638
GRCh38: 2:166238128-166238128
20 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3004G>T (p.Val1002Leu) SNV Conflicting interpretations of pathogenicity 94090 rs4369876 GRCh37: 2:167129256-167129256
GRCh38: 2:166272746-166272746
21 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.5948G>T (p.Ser1983Ile) SNV Uncertain significance 538464 rs770802841 GRCh37: 2:167055201-167055201
GRCh38: 2:166198691-166198691
22 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.5820C>G (p.Asn1940Lys) SNV Uncertain significance 471155 rs371454107 GRCh37: 2:167055329-167055329
GRCh38: 2:166198819-166198819
23 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4820C>T (p.Thr1607Ile) SNV Uncertain significance 130271 rs200470541 GRCh37: 2:167056329-167056329
GRCh38: 2:166199819-166199819
24 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4368C>G (p.Ile1456Met) SNV Uncertain significance 471128 rs1362318488 GRCh37: 2:167083107-167083107
GRCh38: 2:166226597-166226597
25 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3538A>G (p.Asn1180Asp) SNV Uncertain significance 448293 rs750269576 GRCh37: 2:167099101-167099101
GRCh38: 2:166242591-166242591
26 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2351C>G (p.Thr784Ser) SNV Uncertain significance 245859 rs200624920 GRCh37: 2:167134816-167134816
GRCh38: 2:166278306-166278306
27 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2006G>A (p.Arg669His) SNV Uncertain significance 471092 rs200374987 GRCh37: 2:167138287-167138287
GRCh38: 2:166281777-166281777
28 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1604C>T (p.Ser535Leu) SNV Uncertain significance 538480 rs201354321 GRCh37: 2:167141333-167141333
GRCh38: 2:166284823-166284823
29 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1280T>C (p.Leu427Ser) SNV Uncertain significance 234638 rs192406412 GRCh37: 2:167144981-167144981
GRCh38: 2:166288471-166288471
30 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1238T>C (p.Ile413Thr) SNV Uncertain significance 193648 rs200689195 GRCh37: 2:167145023-167145023
GRCh38: 2:166288513-166288513
31 SCN9A NM_001365536.1(SCN9A):c.553C>T (p.Arg185Cys) SNV Uncertain significance 471146 rs202083986 GRCh37: 2:167162345-167162345
GRCh38: 2:166305835-166305835
32 SCN9A NM_001365536.1(SCN9A):c.184A>G (p.Ile62Val) SNV Uncertain significance 6368 rs121908920 GRCh37: 2:167168083-167168083
GRCh38: 2:166311573-166311573
33 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1277T>A (p.Met426Lys) SNV Uncertain significance 415032 rs200415928 GRCh37: 2:167144984-167144984
GRCh38: 2:166288474-166288474
34 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4482A>G (p.Gln1494=) SNV Uncertain significance 626166 rs1558945594 GRCh37: 2:167060891-167060891
GRCh38: 2:166204381-166204381
35 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3767A>G (p.Asn1256Ser) SNV Uncertain significance 130265 rs141268327 GRCh37: 2:167094638-167094638
GRCh38: 2:166238128-166238128
36 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*164G>A SNV Uncertain significance 892578 GRCh37: 2:167055018-167055018
GRCh38: 2:166198508-166198508
37 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*159T>C SNV Uncertain significance 892579 GRCh37: 2:167055023-167055023
GRCh38: 2:166198513-166198513
38 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.5543G>A (p.Arg1848His) SNV Uncertain significance 892606 GRCh37: 2:167055606-167055606
GRCh38: 2:166199096-166199096
39 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4143A>G (p.Arg1381=) SNV Uncertain significance 471123 rs200610689 GRCh37: 2:167085264-167085264
GRCh38: 2:166228754-166228754
40 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4099C>T (p.Arg1367Cys) SNV Uncertain significance 892645 GRCh37: 2:167085308-167085308
GRCh38: 2:166228798-166228798
41 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3265G>A (p.Val1089Met) SNV Uncertain significance 331973 rs886055053 GRCh37: 2:167128995-167128995
GRCh38: 2:166272485-166272485
42 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*226A>C SNV Uncertain significance 331953 rs886055048 GRCh37: 2:167054956-167054956
GRCh38: 2:166198446-166198446
43 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3925-13T>C SNV Uncertain significance 331966 rs886055051 GRCh37: 2:167085495-167085495
GRCh38: 2:166228985-166228985
44 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3754A>G (p.Thr1252Ala) SNV Uncertain significance 331968 rs886055052 GRCh37: 2:167094651-167094651
GRCh38: 2:166238141-166238141
45 SCN9A NM_001365536.1(SCN9A):c.684C>G (p.Ile228Met) SNV Uncertain significance 198153 rs71428908 GRCh37: 2:167160752-167160752
GRCh38: 2:166304242-166304242
46 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3272T>C (p.Ile1091Thr) SNV Uncertain significance 892719 GRCh37: 2:167128988-167128988
GRCh38: 2:166272478-166272478
47 SCN9A NM_001365536.1(SCN9A):c.829C>A (p.Arg277=) SNV Uncertain significance 566530 rs121908916 GRCh37: 2:167159672-167159672
GRCh38: 2:166303162-166303162
48 SCN9A NM_001365536.1(SCN9A):c.822A>G (p.Lys274=) SNV Uncertain significance 538490 rs199784484 GRCh37: 2:167159679-167159679
GRCh38: 2:166303169-166303169
49 SCN9A NM_001365536.1(SCN9A):c.238C>T (p.Pro80Ser) SNV Uncertain significance 892917 GRCh37: 2:167168029-167168029
GRCh38: 2:166311519-166311519
50 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*3202T>C SNV Uncertain significance 892954 GRCh37: 2:167051980-167051980
GRCh38: 2:166195470-166195470

UniProtKB/Swiss-Prot genetic disease variations for Erythermalgia, Primary:

72
# Symbol AA change Variation ID SNP ID
1 SCN9A p.Ile859Thr VAR_019947 rs80356474
2 SCN9A p.Leu869His VAR_019948 rs80356475
3 SCN9A p.Ser241Thr VAR_032014 rs80356470
4 SCN9A p.Phe1460Val VAR_032019 rs80356478
5 SCN9A p.Gln10Arg VAR_064595 rs267607030
6 SCN9A p.Phe216Ser VAR_064598 rs80356469
7 SCN9A p.Asn395Lys VAR_064600 rs80356471
8 SCN9A p.Leu869Phe VAR_064609 rs80356476
9 SCN9A p.Ala1643Glu VAR_072280 rs879253994
10 SCN9A p.Ala1643Thr VAR_072281

Expression for Erythermalgia, Primary

Search GEO for disease gene expression data for Erythermalgia, Primary.

Pathways for Erythermalgia, Primary

GO Terms for Erythermalgia, Primary

Cellular components related to Erythermalgia, Primary according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon GO:0030424 9.13 SCN9A SCN11A SCN10A
2 voltage-gated sodium channel complex GO:0001518 8.8 SCN9A SCN11A SCN10A

Biological processes related to Erythermalgia, Primary according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.63 SCN9A SCN11A SCN10A
2 transmembrane transport GO:0055085 9.61 SCN9A SCN11A SCN10A
3 regulation of ion transmembrane transport GO:0034765 9.5 SCN9A SCN11A SCN10A
4 sodium ion transport GO:0006814 9.43 SCN9A SCN11A SCN10A
5 cation transmembrane transport GO:0098655 9.4 SCN9A SCN10A
6 sensory perception of pain GO:0019233 9.37 SCN9A SCN10A
7 sodium ion transmembrane transport GO:0035725 9.33 SCN9A SCN11A SCN10A
8 neuronal action potential GO:0019228 9.13 SCN9A SCN11A SCN10A
9 membrane depolarization during action potential GO:0086010 8.8 SCN9A SCN11A SCN10A

Molecular functions related to Erythermalgia, Primary according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.5 SCN9A SCN11A SCN10A
2 voltage-gated ion channel activity GO:0005244 9.43 SCN9A SCN11A SCN10A
3 cation channel activity GO:0005261 9.33 SCN9A SCN11A SCN10A
4 sodium channel activity GO:0005272 9.13 SCN9A SCN11A SCN10A
5 voltage-gated sodium channel activity GO:0005248 8.8 SCN9A SCN11A SCN10A

Sources for Erythermalgia, Primary

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
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57 OMIM® (Updated 20-May-2021)
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68 SNOMED-CT via HPO
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