CIP
MCID: IND012
MIFTS: 42

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 57 74 29 6
Insensitivity to Pain, Channelopathy-Associated 57 13
Asymbolia for Pain 57 74
Cip 57 74
Channelopathy-Associated Congenital Insensitivity to Pain 59
Channelopathy-Associated Insensitivity to Pain 74
Congenital Analgesia, Autosomal Recessive 57
Congenital Analgesia Autosomal Recessive 74
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:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity infantile onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 243000
MeSH 44 D000699
MESH via Orphanet 45 D000699 D009477
ICD10 via Orphanet 34 G60.8
UMLS via Orphanet 73 C0002768 C0020075
Orphanet 59 ORPHA88642
MedGen 42 C1855739

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 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 anosmia

UniProtKB/Swiss-Prot : 74 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 top 50) (show all 95)
# Related Disease Score Top Affiliating Genes
1 critical illness polyneuropathy 11.9
2 marsili syndrome 11.6
3 neuropathy, hereditary sensory and autonomic, type v 11.6
4 neuropathy, hereditary sensory and autonomic, type vii 11.4
5 insensitivity to pain, congenital, with anhidrosis 11.2
6 pain sensitivity quantitative trait locus 1 10.6
7 retinoblastoma 10.3
8 familial retinoblastoma 10.3
9 polyneuropathy 10.2
10 breast cancer 10.2
11 leukemia, acute myeloid 10.1
12 lymphoma 10.1
13 hyperparathyroidism 10.1
14 autonomic dysfunction 10.1
15 neuropathy 9.9 SCN9A SCN11A
16 colorectal cancer 9.9
17 fibrosis of extraocular muscles, congenital, 1 9.9
18 ovarian cancer 9.9
19 lung cancer 9.9
20 myeloma, multiple 9.9
21 ocular motor apraxia 9.9
22 pancreatic cancer 9.9
23 testicular germ cell tumor 9.9
24 pituitary adenoma, prolactin-secreting 9.9
25 reflex sympathetic dystrophy 9.9
26 microvascular complications of diabetes 5 9.9
27 leukemia, acute lymphoblastic 9.9
28 myelodysplastic syndrome 9.9
29 hyperprolactinemia 9.9
30 angina pectoris 9.9
31 oral squamous cell carcinoma 9.9
32 bone disease 9.9
33 thyroid lymphoma 9.9
34 lymphocytic leukemia 9.9
35 glucose intolerance 9.9
36 hydrocephalus 9.9
37 borderline personality disorder 9.9
38 respiratory failure 9.9
39 lyme disease 9.9
40 neutropenia 9.9
41 leukemia 9.9
42 dilated cardiomyopathy 9.9
43 gout 9.9
44 algoneurodystrophy 9.9
45 adult-onset still's disease 9.9
46 personality disorder 9.9
47 communicating hydrocephalus 9.9
48 squamous cell carcinoma 9.9
49 hypogonadism 9.9
50 transient cerebral ischemia 9.9

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:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 hypohidrosis 32 HP:0000966
2 anosmia 32 HP:0000458
3 hyporeflexia 32 HP:0001265
4 urinary incontinence 32 HP:0000020
5 hyposmia 32 HP:0004409
6 anhidrosis 32 HP:0000970
7 abnormal autonomic nervous system physiology 32 HP:0012332
8 pain insensitivity 32 HP:0007021
9 painless fractures due to injury 32 HP:0002661

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
anosmia
hyposmia

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
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

Neurologic Central Nervous System:
anosmia
isolated absence of pain sensation
autonomic dysfunction (in patients with hsan2d)

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 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

Articles related to Indifference to Pain, Congenital, Autosomal Recessive:

(show all 27)
# Title Authors PMID Year
1
Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. 8 71
17470132 2007
2
An SCN9A channelopathy causes congenital inability to experience pain. 8 71
17167479 2006
3
Congenital Insensitivity to Pain Overview 71
29419974 2018
4
Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation. 8
23596073 2013
5
Human Mendelian pain disorders: a key to discovery and validation of novel analgesics. 8
22845492 2012
6
Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. 8
21441906 2011
7
Hereditary Sensory and Autonomic Neuropathy Type II 71
21089229 2010
8
Two novel SCN9A mutations causing insensitivity to pain. 8
19304393 2009
9
Double homozygosity for mutations of AGL and SCN9A mimicking neurohepatopathy syndrome. 8
18541889 2008
10
Congenital insensitivity to pain: an update. 8
12583863 2003
11
Not 'indifference to pain' but varieties of hereditary sensory and autonomic neuropathy. 8
6189547 1983
12
[The congenital indifference to pain. 2 futher cases]. 8
4190086 1969
13
Congenital pain asymbolia and auditory imperception. 8
4176404 1968
14
[APROPOS OF A CASE OF CONGENITAL INDIFFERENCE TO PAIN (UNIVERSAL CONGENITAL ANALGESIA). PATHOGENIC HYPOTHESIS]. 8
14177235 1964
15
[CONGENITAL INDIFFERENCE TO PAIN. FAMILIAL CASE; CLINICAL AND BIOLOGICAL PECULIARITIES]. 8
14177236 1964
16
A GENETICAL INVESTIGATION OF CONGENITAL ANALGESIA I. CYTOGENETIC STUDIES. 8
14209604 1964
17
A GENETICAL INVESTIGATION OF CONGENITAL ANALGESIA. II. CLINICO-GENETICAL STUDIES. 8
14209605 1964
18
Chromosome trisomy of group 13-15 in two cases of generalised congenital analgesia. 8
13970027 1963
19
Congenital absence of pain. Report of a case and experimental studies. 8
14007517 1962
20
[Congenital analgia (congenital universal absence of pain)]. 8
13776331 1961
21
Congenital universal insensitivity to pain. 8
13688072 1960
22
Some sensory syndromes in children: indifference to pain and sensory neuropathy. 8
14428406 1959
23
Congenital insensitivity to pain: a neurologic syndrome with bizarre skeletal lesions. 8
13634374 1959
24
[Congenital analgia (congenital generalized pain indifference)]. 8
13448589 1957
25
Congenital insensitivity to pain: a 20 year follow up. 38
7520056 1994
26
[Left pseudothalamic cortical syndrome and pain asymbolia]. 38
1763257 1991
27
Asymbolia for pain: a sensory-limbic disconnection syndrome. 38
3415199 1988

Variations for Indifference to Pain, Congenital, Autosomal Recessive

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

6 (show all 26)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SCN9A NM_002977.3(SCN9A): c.2421_2425del (p.Leu807fs) deletion Pathogenic rs766212849 2:167134709-167134713 2:166278199-166278203
2 SCN9A NM_002977.3(SCN9A): c.4331del (p.Val1444fs) deletion Pathogenic rs1553478584 2:167083111-167083111 2:166226601-166226601
3 SCN9A NM_002977.3(SCN9A): c.1376C> G (p.Ser459Ter) single nucleotide variant Pathogenic rs121908908 2:167143072-167143072 2:166286562-166286562
4 SCN9A SCN9A, 1-BP DEL, 2298T deletion Pathogenic
5 SCN9A NM_002977.3(SCN9A): c.2691G> A (p.Trp897Ter) single nucleotide variant Pathogenic rs121908909 2:167133643-167133643 2:166277133-166277133
6 SCN9A NM_002977.3(SCN9A): c.829C> T (p.Arg277Ter) single nucleotide variant Pathogenic rs121908916 2:167159672-167159672 2:166303162-166303162
7 SCN9A NM_002977.3(SCN9A): c.984C> A (p.Tyr328Ter) single nucleotide variant Pathogenic rs121908917 2:167149864-167149864 2:166293354-166293354
8 SCN9A NM_002977.3(SCN9A): c.2690G> A (p.Trp897Ter) single nucleotide variant Pathogenic rs794729216 2:167133644-167133644 2:166277134-166277134
9 SCN9A NM_002977.3(SCN9A): c.3993delinsTT (p.Leu1331fs) indel Conflicting interpretations of pathogenicity rs606231279 2:167085381-167085381 2:166228871-166228871
10 SCN9A NM_002977.3(SCN9A): c.3734A> G (p.Asn1245Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs141268327 2:167094638-167094638 2:166238128-166238128
11 SCN9A NM_002977.3(SCN9A): c.684C> G (p.Ile228Met) single nucleotide variant Conflicting interpretations of pathogenicity rs71428908 2:167160752-167160752 2:166304242-166304242
12 SCN9A NM_002977.3(SCN9A): c.1277T> A (p.Met426Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs200415928 2:167144984-167144984 2:166288474-166288474
13 SCN9A NM_002977.3(SCN9A): c.1973G> A (p.Arg658His) single nucleotide variant Uncertain significance rs200374987 2:167138287-167138287 2:166281777-166281777
14 SCN9A NM_002977.3(SCN9A): c.5787C> G (p.Asn1929Lys) single nucleotide variant Uncertain significance rs371454107 2:167055329-167055329 2:166198819-166198819
15 SCN9A NM_002977.3(SCN9A): c.4335C> G (p.Ile1445Met) single nucleotide variant Uncertain significance rs1362318488 2:167083107-167083107 2:166226597-166226597
16 SCN9A NM_002977.3(SCN9A): c.5915G> T (p.Ser1972Ile) single nucleotide variant Uncertain significance rs770802841 2:167055201-167055201 2:166198691-166198691
17 SCN9A NM_002977.3(SCN9A): c.1604C> T (p.Ser535Leu) single nucleotide variant Uncertain significance rs201354321 2:167141333-167141333 2:166284823-166284823
18 SCN9A NM_002977.3(SCN9A): c.553C> T (p.Arg185Cys) single nucleotide variant Uncertain significance rs202083986 2:167162345-167162345 2:166305835-166305835
19 SCN9A NM_002977.3(SCN9A): c.184A> G (p.Ile62Val) single nucleotide variant Uncertain significance rs121908920 2:167168083-167168083 2:166311573-166311573
20 SCN9A NM_002977.3(SCN9A): c.4787C> T (p.Thr1596Ile) single nucleotide variant Uncertain significance rs200470541 2:167056329-167056329 2:166199819-166199819
21 SCN9A NM_002977.3(SCN9A): c.1238T> C (p.Ile413Thr) single nucleotide variant Uncertain significance rs200689195 2:167145023-167145023 2:166288513-166288513
22 SCN9A NM_002977.3(SCN9A): c.1285C> T (p.Arg429Cys) single nucleotide variant Uncertain significance rs763256222 2:167144976-167144976 2:166288466-166288466
23 SCN9A NM_002977.3(SCN9A): c.3505A> G (p.Asn1169Asp) single nucleotide variant Uncertain significance rs750269576 2:167099101-167099101 2:166242591-166242591
24 SCN9A NM_002977.3(SCN9A): c.1280T> C (p.Leu427Ser) single nucleotide variant Uncertain significance rs192406412 2:167144981-167144981 2:166288471-166288471
25 SCN9A NM_002977.3(SCN9A): c.2318C> G (p.Thr773Ser) single nucleotide variant Uncertain significance rs200624920 2:167134816-167134816 2:166278306-166278306
26 SCN9A NM_002977.3(SCN9A): c.4449A> G (p.Gln1483=) single nucleotide variant Uncertain significance 2:167060891-167060891 2:166204381-166204381

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

74
# Symbol AA change Variation ID SNP ID
1 SCN9A p.Arg907Gln VAR_064610 rs102415236

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 SCN9A SCN11A SCN10A
2
Show member pathways
12.45 SCN9A SCN11A SCN10A
3
Show member pathways
12.27 SCN9A SCN11A SCN10A
4
Show member pathways
12.09 SCN9A SCN11A SCN10A
5 11.97 SCN9A SCN11A SCN10A
6
Show member pathways
11.43 SCN9A SCN11A SCN10A
7
Show member pathways
11.01 SCN9A SCN11A SCN10A
8 10.28 SCN9A SCN11A SCN10A

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 SCN9A SCN11A SCN10A
2 voltage-gated sodium channel complex GO:0001518 8.8 SCN9A SCN11A SCN10A

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 SCN9A SCN11A SCN10A
2 transmembrane transport GO:0055085 9.58 SCN9A SCN11A SCN10A
3 regulation of ion transmembrane transport GO:0034765 9.5 SCN9A SCN11A SCN10A
4 ion transmembrane transport GO:0034220 9.46 SCN9A SCN10A
5 sodium ion transport GO:0006814 9.43 SCN9A SCN11A 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 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 SCN9A SCN11A SCN10A
2 voltage-gated ion channel activity GO:0005244 9.33 SCN9A SCN11A SCN10A
3 sodium channel activity GO:0005272 9.13 SCN9A SCN11A SCN10A
4 voltage-gated sodium channel activity GO:0005248 8.8 SCN9A SCN11A SCN10A

Sources for Indifference to Pain, Congenital, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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