CIP
MCID: IND012
MIFTS: 36

Indifference to Pain, Congenital, Autosomal Recessive (CIP)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Indifference to Pain, Congenital, Autosomal Recessive

MalaCards integrated aliases for Indifference to Pain, Congenital, Autosomal Recessive:

Name: Indifference to Pain, Congenital, Autosomal Recessive 58 76 30 6
Insensitivity to Pain, Channelopathy-Associated 58 13
Asymbolia for Pain 58 76
Cip 58 76
Channelopathy-Associated Congenital Insensitivity to Pain 60
Channelopathy-Associated Insensitivity to Pain 76
Congenital Analgesia, Autosomal Recessive 58
Congenital Analgesia Autosomal Recessive 76
Insensitivity to Pain, Congenital 58
Channelopathy-Associated Cip 60
Hsan2d, Autosomal Recessive 58

Characteristics:

Orphanet epidemiological data:

60
channelopathy-associated congenital insensitivity to pain
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or childhood
variable severity (in patients with hsan2d)
affected individuals are highly prone to burn-related injuries


HPO:

33
indifference to pain, congenital, autosomal recessive:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

OMIM 58 243000
MeSH 45 D000699
MESH via Orphanet 46 D000699 D009477
ICD10 via Orphanet 35 G60.8
UMLS via Orphanet 75 C0002768 C0020075
Orphanet 60 ORPHA88642
MedGen 43 C1855739

Summaries for Indifference to Pain, Congenital, Autosomal Recessive

OMIM : 58 Congenital indifference to pain is a rare autosomal recessive disorder characterized by the complete absence of pain perception typically associated with noxious stimuli. Affected individuals are aware of a stimulus, but have lost the ability to perceive pain. Most patients are hyposmic or anosmic. Other sensory modalities are unaffected, and there is an absence of overt autonomic symptoms. Sural nerve biopsy and nerve conduction velocity studies are normal (summary by Cox et al., 2006; and Goldberg et al., 2012). Hereditary sensory and autonomic neuropathy type IID (HSAN2D) is an autosomal recessive disorder characterized by congenital or childhood-onset distal loss of pain and temperature sensation as well as autonomic dysfunction accompanied by hyposmia, hearing loss, hypogeusia, and sometimes bone dysplasia. The phenotype is highly variable, even within families. Two Japanese families have been reported (summary by Yuan et al., 2013). For a discussion of genetic heterogeneity of HSAN, see HSAN1 (162400). (243000)

MalaCards based summary : Indifference to Pain, Congenital, Autosomal Recessive, also known as insensitivity to pain, channelopathy-associated, is related to critical illness polyneuropathy and marsili syndrome. An important gene associated with Indifference to Pain, Congenital, Autosomal Recessive is SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9), and among its related pathways/superpathways are Developmental Biology and G-Beta Gamma Signaling. Affiliated tissues include bone and tongue, and related phenotypes are hypohidrosis and hyporeflexia

UniProtKB/Swiss-Prot : 76 Indifference to pain, congenital, autosomal recessive: A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating.

Related Diseases for Indifference to Pain, Congenital, Autosomal Recessive

Diseases related to Indifference to Pain, Congenital, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 critical illness polyneuropathy 11.8
2 marsili syndrome 11.5
3 neuropathy, hereditary sensory and autonomic, type v 11.5
4 neuropathy, hereditary sensory and autonomic, type vii 11.2
5 insensitivity to pain, congenital, with anhidrosis 11.1
6 breast cancer 10.0
7 polyneuropathy 10.0
8 squamous cell carcinoma 10.0
9 ovarian cancer 9.9
10 retinoblastoma 9.9
11 lung cancer 9.9
12 pancreatic cancer 9.9
13 testicular germ cell tumor 9.9
14 testicular germ cell tumor 1 9.9
15 hyperprolactinemia 9.9
16 angina pectoris 9.9
17 b-cell lymphomas 9.9
18 chronic kidney failure 9.9
19 oral squamous cell carcinoma 9.9
20 lymphoma 9.9
21 bone disease 9.9
22 respiratory failure 9.9
23 adult-onset still's disease 9.9
24 transient cerebral ischemia 9.9
25 dyskeratosis congenita 9.9
26 ischemia 9.9
27 infertility 9.9
28 kidney disease 9.9
29 lymphosarcoma 9.9
30 bowenoid papulosis 9.9
31 germ cells tumors 9.9
32 mycobacterium abscessus 9.9
33 ovarian epithelial cancer 9.9
34 hypoxia 9.9
35 complication after organ transplantation 9.9
36 generalized epilepsy with febrile seizures plus, type 7 9.9 SCN1A-AS1 SCN9A
37 trigeminal neuralgia 9.8 SCN10A SCN9A
38 generalized epilepsy with febrile seizures plus 9.8 SCN1A-AS1 SCN9A
39 neuropathy 9.8 SCN11A SCN9A
40 erythromelalgia 9.8 SCN10A SCN9A
41 causalgia 9.5 SCN10A SCN11A
42 sodium channelopathy-related small fiber neuropathy 9.5 SCN9A SCN11A SCN10A
43 erythermalgia, primary 9.5 SCN9A SCN11A SCN10A
44 paine syndrome 9.5 SCN10A SCN11A SCN9A
45 paroxysmal extreme pain disorder 9.1 SCN9A SCN1A-AS1 SCN11A SCN10A

Graphical network of the top 20 diseases related to Indifference to Pain, Congenital, Autosomal Recessive:



Diseases related to Indifference to Pain, Congenital, Autosomal Recessive

Symptoms & Phenotypes for Indifference to Pain, Congenital, Autosomal Recessive

Human phenotypes related to Indifference to Pain, Congenital, Autosomal Recessive:

33 (show all 9)
# Description HPO Frequency HPO Source Accession
1 hypohidrosis 33 HP:0000966
2 hyporeflexia 33 HP:0001265
3 urinary incontinence 33 HP:0000020
4 anosmia 33 HP:0000458
5 hyposmia 33 HP:0004409
6 anhidrosis 33 HP:0000970
7 abnormal autonomic nervous system physiology 33 HP:0012332
8 pain insensitivity 33 HP:0007021
9 painless fractures due to injury 33 HP:0002661

Symptoms via clinical synopsis from OMIM:

58
Neurologic Peripheral Nervous System:
hyporeflexia
isolated absence of pain sensation
temperature sensation may be diminished
all other sensory modalities are intact
normal peripheral nerve biopsy
more
Neurologic Central Nervous System:
anosmia
isolated absence of pain sensation
autonomic dysfunction (in patients with hsan2d)

Head And Neck Ears:
hearing impairment, asymmetric (in some patients with hsan2d)

Genitourinary Bladder:
urinary incontinence (in some patients with hsan2d)

Skeletal Feet:
ulceration of digits

Laboratory Abnormalities:
normal axonal flare response after intradermal histamine injection

Head And Neck Nose:
anosmia
hyposmia

Skeletal:
painless fractures due to injury
neuropathic joints
bone deformities resulting from untreated fractures
bone dysplasia (in some patients)

Head And Neck Mouth:
reduced numbers of tongue fungiform papilla (in some patients with hsan2d)

Skeletal Hands:
ulceration of digits

Skin Nails Hair Skin:
distal painless ulcers
hypohidrosis (in patients with hsan2d)
anhidrosis (in patients with hsan2d)

Clinical features from OMIM:

243000

Drugs & Therapeutics for Indifference to Pain, Congenital, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Indifference to Pain, Congenital, Autosomal Recessive

Genetic Tests for Indifference to Pain, Congenital, Autosomal Recessive

Genetic tests related to Indifference to Pain, Congenital, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Indifference to Pain, Congenital, Autosomal Recessive 30 SCN9A

Anatomical Context for Indifference to Pain, Congenital, Autosomal Recessive

MalaCards organs/tissues related to Indifference to Pain, Congenital, Autosomal Recessive:

42
Bone, Tongue

Publications for Indifference to Pain, Congenital, Autosomal Recessive

Variations for Indifference to Pain, Congenital, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Indifference to Pain, Congenital, Autosomal Recessive:

76
# Symbol AA change Variation ID SNP ID
1 SCN9A p.Arg907Gln VAR_064610 rs102415236

ClinVar genetic disease variations for Indifference to Pain, Congenital, Autosomal Recessive:

6 (show all 21)
# Gene Variation Type Significance SNP ID Assembly Location
1 SCN9A NM_002977.3(SCN9A): c.3993delGinsTT (p.Leu1331Phefs) indel Pathogenic rs606231279 GRCh37 Chromosome 2, 167085381: 167085381
2 SCN9A NM_002977.3(SCN9A): c.3993delGinsTT (p.Leu1331Phefs) indel Pathogenic rs606231279 GRCh38 Chromosome 2, 166228871: 166228871
3 SCN9A NM_002977.3(SCN9A): c.684C> G (p.Ile228Met) single nucleotide variant Conflicting interpretations of pathogenicity rs71428908 GRCh37 Chromosome 2, 167160752: 167160752
4 SCN9A NM_002977.3(SCN9A): c.684C> G (p.Ile228Met) single nucleotide variant Conflicting interpretations of pathogenicity rs71428908 GRCh38 Chromosome 2, 166304242: 166304242
5 SCN9A NM_002977.3(SCN9A): c.2690G> A (p.Trp897Ter) single nucleotide variant Pathogenic rs794729216 GRCh37 Chromosome 2, 167133644: 167133644
6 SCN9A NM_002977.3(SCN9A): c.2690G> A (p.Trp897Ter) single nucleotide variant Pathogenic rs794729216 GRCh38 Chromosome 2, 166277134: 166277134
7 SCN9A NM_002977.3(SCN9A): c.1376C> G (p.Ser459Ter) single nucleotide variant Pathogenic rs121908908 GRCh37 Chromosome 2, 167143072: 167143072
8 SCN9A NM_002977.3(SCN9A): c.1376C> G (p.Ser459Ter) single nucleotide variant Pathogenic rs121908908 GRCh38 Chromosome 2, 166286562: 166286562
9 SCN9A SCN9A, 1-BP DEL, 2298T deletion Pathogenic
10 SCN9A NM_002977.3(SCN9A): c.2691G> A (p.Trp897Ter) single nucleotide variant Pathogenic rs121908909 GRCh37 Chromosome 2, 167133643: 167133643
11 SCN9A NM_002977.3(SCN9A): c.2691G> A (p.Trp897Ter) single nucleotide variant Pathogenic rs121908909 GRCh38 Chromosome 2, 166277133: 166277133
12 SCN9A NM_002977.3(SCN9A): c.829C> T (p.Arg277Ter) single nucleotide variant Pathogenic rs121908916 GRCh37 Chromosome 2, 167159672: 167159672
13 SCN9A NM_002977.3(SCN9A): c.829C> T (p.Arg277Ter) single nucleotide variant Pathogenic rs121908916 GRCh38 Chromosome 2, 166303162: 166303162
14 SCN9A NM_002977.3(SCN9A): c.984C> A (p.Tyr328Ter) single nucleotide variant Pathogenic rs121908917 GRCh37 Chromosome 2, 167149864: 167149864
15 SCN9A NM_002977.3(SCN9A): c.984C> A (p.Tyr328Ter) single nucleotide variant Pathogenic rs121908917 GRCh38 Chromosome 2, 166293354: 166293354
16 SCN9A NM_002977.3(SCN9A): c.2421_2425delAAGTT (p.Leu807Phefs) deletion Pathogenic rs766212849 GRCh37 Chromosome 2, 167134709: 167134713
17 SCN9A NM_002977.3(SCN9A): c.2421_2425delAAGTT (p.Leu807Phefs) deletion Pathogenic rs766212849 GRCh38 Chromosome 2, 166278199: 166278203
18 SCN9A NM_002977.3(SCN9A): c.4331delT (p.Val1444Alafs) deletion Pathogenic rs1553478584 GRCh37 Chromosome 2, 167083111: 167083111
19 SCN9A NM_002977.3(SCN9A): c.4331delT (p.Val1444Alafs) deletion Pathogenic rs1553478584 GRCh38 Chromosome 2, 166226601: 166226601
20 SCN9A NM_002977.3(SCN9A): c.1285C> T (p.Arg429Cys) single nucleotide variant Uncertain significance rs763256222 GRCh37 Chromosome 2, 167144976: 167144976
21 SCN9A NM_002977.3(SCN9A): c.1285C> T (p.Arg429Cys) single nucleotide variant Uncertain significance rs763256222 GRCh38 Chromosome 2, 166288466: 166288466

Expression for Indifference to Pain, Congenital, Autosomal Recessive

Search GEO for disease gene expression data for Indifference to Pain, Congenital, Autosomal Recessive.

Pathways for Indifference to Pain, Congenital, Autosomal Recessive

Pathways related to Indifference to Pain, Congenital, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.82 SCN10A SCN11A SCN9A
2
Show member pathways
12.5 SCN10A SCN11A SCN9A
3
Show member pathways
12.27 SCN10A SCN11A SCN9A
4
Show member pathways
12.09 SCN10A SCN11A SCN9A
5 11.97 SCN10A SCN11A SCN9A
6
Show member pathways
11.43 SCN10A SCN11A SCN9A
7
Show member pathways
11.01 SCN10A SCN11A SCN9A
8 10.28 SCN10A SCN11A SCN9A

GO Terms for Indifference to Pain, Congenital, Autosomal Recessive

Cellular components related to Indifference to Pain, Congenital, Autosomal Recessive according to GeneCards Suite gene sharing:

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

Biological processes related to Indifference to Pain, Congenital, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.61 SCN10A SCN11A SCN9A
2 transmembrane transport GO:0055085 9.58 SCN10A SCN11A SCN9A
3 regulation of ion transmembrane transport GO:0034765 9.5 SCN10A SCN11A SCN9A
4 ion transmembrane transport GO:0034220 9.46 SCN10A SCN9A
5 sodium ion transport GO:0006814 9.43 SCN10A SCN11A SCN9A
6 sensory perception of pain GO:0019233 9.37 SCN10A SCN9A
7 sodium ion transmembrane transport GO:0035725 9.33 SCN10A SCN11A SCN9A
8 neuronal action potential GO:0019228 9.13 SCN10A SCN11A SCN9A
9 membrane depolarization during action potential GO:0086010 8.8 SCN10A SCN11A SCN9A

Molecular functions related to Indifference to Pain, Congenital, Autosomal Recessive according to GeneCards Suite gene sharing:

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

Sources for Indifference to Pain, Congenital, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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