MCID: PRX015
MIFTS: 46

Paroxysmal Extreme Pain Disorder

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Paroxysmal Extreme Pain Disorder

MalaCards integrated aliases for Paroxysmal Extreme Pain Disorder:

Name: Paroxysmal Extreme Pain Disorder 53 49 24 55 71 36 28 13 69
Familial Rectal Pain 49 24 55 71
Pepd 53 49 24 71
Pexpd 53 49 24
Submandibular, Ocular, and Rectal Pain with Flushing 49 24
Pain, Submandibular, Ocular, and Rectal, with Flushing 53
Paroxysmal Extreme Pain Disorder, 53
Familial Rectal Syndrome 49
Rectal Pain, Familial 53
Pexpd; Pepd 53
Frp 71

Characteristics:

Orphanet epidemiological data:

55
paroxysmal extreme pain disorder
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
onset in neonatal period or infancy
presents with 4 types of painful episodes - (1) birth crisis, babies are born red and stiff (2) rectal crisis, triggered by defecation or emotional factors (3) ocular crisis (4) mandibular crisis, triggered by eating or yawning
attacks tend to decrease with age
allelic disorder to primary erythermalgia


HPO:

31
paroxysmal extreme pain disorder:
Onset and clinical course neonatal onset
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


External Ids:

OMIM 53 167400
Orphanet 55 ORPHA46348
UMLS via Orphanet 70 C1833661
MedGen 39 C1833661
KEGG 36 H00772
UMLS 69 C1833661

Summaries for Paroxysmal Extreme Pain Disorder

NIH Rare Diseases : 49 Paroxysmal extreme pain disorder is a form of peripheral neuropathy characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. Early in life, the pain is often concentrated in the lower part of the body and may be triggered by a bowel movement. As a person ages, the location of the pain may change, with attacks affecting the head and face. Triggers of these pain attacks include changes in temperature, emotional distress or eating spicy foods and drinking cold beverages. Paroxysmal extreme pain disorder is caused by mutations  in the SCN9A gene. This condition is inherited in an autosomal dominant pattern. Treatment may include medications used to manage chronic neuropathic pain (anticonvulsants) such as the sodium channel blocker carbamazepine.  Last updated: 12/3/2015

MalaCards based summary : Paroxysmal Extreme Pain Disorder, also known as familial rectal pain, is related to erythromelalgia and paine syndrome, and has symptoms including constipation, seizures and anal pain. An important gene associated with Paroxysmal Extreme Pain Disorder is SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and Developmental Biology. Affiliated tissues include skin and testes, and related phenotypes are integument and taste/olfaction

OMIM : 53 Paroxysmal extreme pain disorder, formerly known as familial rectal pain, is characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. Onset is usually in the neonatal period or infancy (Fertleman et al., 2006). (167400)

UniProtKB/Swiss-Prot : 71 Paroxysmal extreme pain disorder: Autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing.

Genetics Home Reference : 24 Paroxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea).

Wikipedia : 72 Paroxysmal extreme pain disorder (PEPD), originally named familial rectal pain syndrome, is a rare... more...

Related Diseases for Paroxysmal Extreme Pain Disorder

Diseases related to Paroxysmal Extreme Pain Disorder via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 erythromelalgia 29.6 SCN10A SCN4B SCN9A
2 paine syndrome 29.2 SCN10A SCN11A SCN9A TRPV1
3 prolidase deficiency 12.0
4 bacterial vaginosis 11.1
5 legg-calve-perthes disease 11.1
6 brittle bone disorder 11.1
7 hypermobility syndrome 11.1
8 osteogenesis imperfecta, type i 11.0
9 griscelli syndrome, type 1 11.0
10 osteogenesis imperfecta, type iii 11.0
11 sexual sadism 11.0
12 cutaneous solitary mastocytoma 11.0
13 episodic pain syndrome, familial, 1 10.4
14 rheumatoid arthritis 10.0
15 arthritis 10.0
16 neuronitis 10.0
17 burning mouth syndrome 9.9 SCN9A TRPV1
18 mononeuritis of lower limb 9.9 SCN10A TRPV1
19 lesion of sciatic nerve 9.9 SCN10A TRPV1
20 sciatic neuropathy 9.9 SCN10A TRPV1
21 hematopoietic stem cell transplantation 9.9
22 pediatric ependymoma 9.9
23 ependymoma 9.9
24 hyper ige syndrome 9.9
25 osteoarthritis with mild chondrodysplasia 9.9
26 osteoarthritis 9.9
27 glioma 9.9
28 somatoform disorder 9.9 SCN9A TRPV1
29 allergic hypersensitivity disease 9.8
30 headache 9.8
31 peripheral nervous system disease 9.8 SCN9A TRPV1
32 neuroma 9.8 SCN10A TRPV1
33 diabetic neuropathy 9.7 SCN9A TRPV1
34 dental pulp disease 9.6 SCN11A TRPV1
35 brugada syndrome 9.6 SCN10A SCN4B
36 sodium channelopathy-related small fiber neuropathy 9.5 SCN10A SCN11A SCN9A
37 erythermalgia, primary 9.5 SCN10A SCN11A SCN9A
38 indifference to pain, congenital, autosomal recessive 9.5 SCN10A SCN11A SCN9A
39 trigeminal nerve disease 9.4 SCN11A SCN9A TRPV1
40 trigeminal neuralgia 9.0 SCN10A SCN11A SCN9A TRPV1

Graphical network of the top 20 diseases related to Paroxysmal Extreme Pain Disorder:



Diseases related to Paroxysmal Extreme Pain Disorder

Symptoms & Phenotypes for Paroxysmal Extreme Pain Disorder

Symptoms via clinical synopsis from OMIM:

53
Cardiovascular Heart:
tachycardia
bradycardia
autonomic reflex asystolic syncopal events

Head And Neck Eyes:
lacrimation, episodic
ocular pain, episodic

Neurologic Peripheral Nervous System:
autonomic reflex asystolic syncopal events
burning pain, episodic
nonepileptic tonic attacks (most common in infants and young children)

Genitourinary Bladder:
painful micturition (in some patients)

Head And Neck Face:
mandibular and submandibular pain, episodic, triggered by eating and yawning

Head And Neck Nose:
rhinorrhea, episodic

Abdomen Gastroin testinal:
rectal pain, episodic, triggered by defecation

Skin Nails Hair Skin:
reddish discoloration, episodic, associated with pain
skin flushing, episodic, associated with pain


Clinical features from OMIM:

167400

Human phenotypes related to Paroxysmal Extreme Pain Disorder:

55 31 (show all 9)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 constipation 55 31 frequent (33%) Frequent (79-30%) HP:0002019
2 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
3 anal pain 31 HP:0500005
4 impaired pain sensation 31 HP:0007328
5 lacrimation abnormality 31 HP:0000632
6 tachycardia 31 HP:0001649
7 ocular pain 31 HP:0200026
8 bradycardia 31 HP:0001662
9 mandibular pain 31 HP:0200025

UMLS symptoms related to Paroxysmal Extreme Pain Disorder:


pain

MGI Mouse Phenotypes related to Paroxysmal Extreme Pain Disorder:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.26 SCN10A SCN11A SCN9A TRPV1
2 taste/olfaction MP:0005394 8.62 SCN9A TRPV1

Drugs & Therapeutics for Paroxysmal Extreme Pain Disorder

Search Clinical Trials , NIH Clinical Center for Paroxysmal Extreme Pain Disorder

Genetic Tests for Paroxysmal Extreme Pain Disorder

Genetic tests related to Paroxysmal Extreme Pain Disorder:

# Genetic test Affiliating Genes
1 Paroxysmal Extreme Pain Disorder 28 SCN9A

Anatomical Context for Paroxysmal Extreme Pain Disorder

MalaCards organs/tissues related to Paroxysmal Extreme Pain Disorder:

38
Skin, Testes

Publications for Paroxysmal Extreme Pain Disorder

Articles related to Paroxysmal Extreme Pain Disorder:

(show all 17)
# Title Authors Year
1
Advanced Genetic Testing Comes to the Pain Clinic to Make a Diagnosis of Paroxysmal Extreme Pain Disorder. ( 27525141 )
2016
2
Short-lasting unilateral neuralgiform headache attacks with ispilateral facial flushing is a new variant of paroxysmal extreme pain disorder. ( 25903274 )
2015
3
Bilateral congenital corneal anesthesia in a patient with SCN9A mutation, confirmed primary erythromelalgia, and paroxysmal extreme pain disorder. ( 26486037 )
2015
4
What are the treatment options for paroxysmal extreme pain disorder? ( 26059255 )
2015
5
p.L1612P, a Novel Voltage-gated Sodium Channel Nav1.7 Mutation Inducing a Cold Sensitive Paroxysmal Extreme Pain Disorder. ( 25285947 )
2014
6
Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder. ( 24817410 )
2014
7
Paroxysmal extreme pain disorder. ( 23599527 )
2013
8
Paroxysmal extreme pain disorder: a molecular lesion of peripheral neurons. ( 21079636 )
2011
9
Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navbeta4 peptide-mediated resurgent sodium currents. ( 21115638 )
2011
10
Case reports: anesthesia for a patient with paroxysmal extreme pain disorder. ( 20435947 )
2010
11
NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. ( 18945915 )
2008
12
Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable. ( 18803825 )
2008
13
Paroxysmal extreme pain disorder mutations within the D3/S4-S5 linker of Nav1.7 cause moderate destabilization of fast inactivation. ( 18599537 )
2008
14
Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). ( 17679678 )
2007
15
Voltage-gated ion channel Nav1.7 innervation in patients with idiopathic rectal hypersensitivity and paroxysmal extreme pain disorder (familial rectal pain). ( 17928139 )
2007
16
What's in a name--familial rectal pain syndrome becomes paroxysmal extreme pain disorder. ( 17043302 )
2006
17
SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. ( 17145499 )
2006

Variations for Paroxysmal Extreme Pain Disorder

UniProtKB/Swiss-Prot genetic disease variations for Paroxysmal Extreme Pain Disorder:

71
# Symbol AA change Variation ID SNP ID
1 SCN9A p.Arg1007Cys VAR_032015 rs121908910
2 SCN9A p.Val1309Asp VAR_032016 rs121908911
3 SCN9A p.Val1309Phe VAR_032017 rs121908912
4 SCN9A p.Val1310Phe VAR_032018 rs121908913
5 SCN9A p.Ile1472Thr VAR_032020 rs121908914
6 SCN9A p.Phe1473Val VAR_032021
7 SCN9A p.Thr1475Ile VAR_032022 rs121908915
8 SCN9A p.Met1638Lys VAR_032023
9 SCN9A p.Leu1623Pro VAR_072279
10 SCN9A p.Ala1643Glu VAR_072280 rs879253994

ClinVar genetic disease variations for Paroxysmal Extreme Pain Disorder:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SCN9A NM_002977.3(SCN9A): c.2986C> T (p.Arg996Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121908910 GRCh37 Chromosome 2, 167129241: 167129241
2 SCN9A NM_002977.3(SCN9A): c.3893T> A (p.Val1298Asp) single nucleotide variant Pathogenic rs121908911 GRCh37 Chromosome 2, 167085481: 167085481
3 SCN9A NM_002977.3(SCN9A): c.3892G> T (p.Val1298Phe) single nucleotide variant Pathogenic rs121908912 GRCh37 Chromosome 2, 167085482: 167085482
4 SCN9A NM_002977.3(SCN9A): c.3895G> T (p.Val1299Phe) single nucleotide variant Pathogenic rs121908913 GRCh37 Chromosome 2, 167085479: 167085479
5 SCN9A NM_002977.3(SCN9A): c.4382T> C (p.Ile1461Thr) single nucleotide variant Pathogenic rs121908914 GRCh37 Chromosome 2, 167060958: 167060958
6 SCN9A NM_002977.3(SCN9A): c.4391C> T (p.Thr1464Ile) single nucleotide variant Pathogenic rs121908915 GRCh37 Chromosome 2, 167060949: 167060949
7 SCN9A NM_002977.3(SCN9A): c.4895C> A (p.Ala1632Glu) single nucleotide variant Pathogenic rs879253994 GRCh37 Chromosome 2, 167056221: 167056221

Expression for Paroxysmal Extreme Pain Disorder

Search GEO for disease gene expression data for Paroxysmal Extreme Pain Disorder.

Pathways for Paroxysmal Extreme Pain Disorder

Pathways related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.01 SCN10A SCN11A SCN4B SCN9A
2
Show member pathways
12.95 SCN10A SCN11A SCN4B SCN9A
3
Show member pathways
12.54 SCN10A SCN11A SCN4B SCN9A
4
Show member pathways
12.35 SCN10A SCN11A SCN4B SCN9A
5
Show member pathways
12.15 SCN10A SCN11A SCN4B SCN9A
6 12.11 SCN10A SCN11A SCN9A
7
Show member pathways
11.55 SCN10A SCN11A SCN4B SCN9A
8
Show member pathways
11.13 SCN10A SCN11A SCN4B SCN9A
9 10.4 SCN10A SCN11A SCN4B SCN9A

GO Terms for Paroxysmal Extreme Pain Disorder

Cellular components related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.55 SCN10A SCN11A SCN4B SCN9A TRPV1
2 intrinsic component of plasma membrane GO:0031226 8.96 SCN4B TRPV1
3 voltage-gated sodium channel complex GO:0001518 8.92 SCN10A SCN11A SCN4B SCN9A

Biological processes related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.89 SCN10A SCN11A SCN4B SCN9A TRPV1
2 transmembrane transport GO:0055085 9.81 SCN10A SCN11A SCN9A TRPV1
3 ion transport GO:0006811 9.72 SCN10A SCN11A SCN4B SCN9A TRPV1
4 ion transmembrane transport GO:0034220 9.7 SCN11A SCN9A TRPV1
5 regulation of ion transmembrane transport GO:0034765 9.67 SCN10A SCN11A SCN4B SCN9A
6 sensory perception of pain GO:0019233 9.61 SCN10A SCN9A TRPV1
7 neuronal action potential GO:0019228 9.58 SCN10A SCN11A SCN9A
8 behavioral response to pain GO:0048266 9.48 SCN9A TRPV1
9 AV node cell action potential GO:0086016 9.46 SCN10A SCN4B
10 sodium ion transport GO:0006814 9.46 SCN10A SCN11A SCN4B SCN9A
11 membrane depolarization during action potential GO:0086010 9.43 SCN10A SCN11A SCN9A
12 sodium ion transmembrane transport GO:0035725 9.26 SCN10A SCN11A SCN4B SCN9A
13 regulation of postsynaptic membrane potential GO:0060078 8.92 SCN10A SCN11A SCN4B SCN9A

Molecular functions related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 voltage-gated ion channel activity GO:0005244 9.56 SCN10A SCN11A SCN4B SCN9A
2 ion channel activity GO:0005216 9.46 SCN10A SCN11A SCN9A TRPV1
3 ion channel binding GO:0044325 9.32 SCN10A SCN4B
4 sodium channel activity GO:0005272 9.26 SCN10A SCN11A SCN4B SCN9A
5 voltage-gated sodium channel activity GO:0005248 8.92 SCN10A SCN11A SCN4B SCN9A

Sources for Paroxysmal Extreme Pain Disorder

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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