MCID: IND012
MIFTS: 35

Indifference to Pain, Congenital, Autosomal Recessive

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 57 75 29 6
Insensitivity to Pain, Channelopathy-Associated 57 13
Asymbolia for Pain 57 75
Cip 57 75
Channelopathy-Associated Congenital Insensitivity to Pain 59
Channelopathy-Associated Insensitivity to Pain 75
Congenital Analgesia, Autosomal Recessive 57
Congenital Analgesia Autosomal Recessive 75
Insensitivity to Pain, Congenital 57
Channelopathy-Associated Cip 59
Hsan2d, Autosomal Recessive 57

Characteristics:

Orphanet epidemiological data:

59
channelopathy-associated congenital insensitivity to pain
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
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:

32
indifference to pain, congenital, autosomal recessive:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 243000
Orphanet 59 ORPHA88642
MESH via Orphanet 45 D000699 D009477
UMLS via Orphanet 74 C0002768 C0020075
ICD10 via Orphanet 34 G60.8
MedGen 42 C1855739
MeSH 44 D000699

Summaries for Indifference to Pain, Congenital, Autosomal Recessive

OMIM : 57 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 insensitivity to pain, congenital, with anhidrosis and critical illness polyneuropathy. 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 urinary incontinence and anosmia

UniProtKB/Swiss-Prot : 75 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

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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 urinary incontinence 32 HP:0000020
2 anosmia 32 HP:0000458
3 hypohidrosis 32 HP:0000966
4 anhidrosis 32 HP:0000970
5 hyporeflexia 32 HP:0001265
6 dysautonomia 32 HP:0002459
7 painless fractures due to injury 32 HP:0002661
8 hyposmia 32 HP:0004409
9 pain insensitivity 32 HP:0007021

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 29 SCN9A

Anatomical Context for Indifference to Pain, Congenital, Autosomal Recessive

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

41
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:

75
# Symbol AA change Variation ID SNP ID
1 SCN9A p.Arg907Gln VAR_064610 rs1024152367Indifference

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

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

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
12.45 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 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 SCN11A 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 membrane depolarization during action potential GO:0086010 9.13 SCN10A SCN11A SCN9A
9 neuronal action potential GO:0019228 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 9.5 SCN10A SCN11A SCN9A
2 voltage-gated ion channel activity GO:0005244 9.43 SCN10A SCN11A SCN9A
3 cation channel activity GO:0005261 9.33 SCN10A SCN11A SCN9A
4 sodium channel activity GO:0005272 9.13 SCN10A SCN11A SCN9A
5 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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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