CCHS
MCID: CNT091
MIFTS: 51

Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease (CCHS) malady

Genetic diseases, Neuronal diseases, Fetal diseases, Rare diseases categories
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Summaries for Central Hypoventilation Syndrome, Congenital, with or Without...

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Genetics Home Reference:21 Congenital central hypoventilation syndrome (CCHS) is a disorder that affects breathing. People with this disorder take shallow breaths (hypoventilate), especially during sleep, resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. Ordinarily, the part of the nervous system that controls involuntary body processes (autonomic nervous system) would react to such an imbalance by stimulating the individual to breathe more deeply or wake up. This reaction is impaired in people with CCHS, and they must be supported with a machine to help them breathe (mechanical ventilation) or a device that stimulates a normal breathing pattern (diaphragm pacemaker). Some affected individuals need this support 24 hours a day, while others need it only at night.

MalaCards based summary: Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease, also known as congenital central alveolar hypoventilation syndrome, is related to central hypoventilation syndrome and hirschsprung's disease, and has symptoms including dolichocolon/megacolon/megadolichocolon/hirschsprung's disease, respiratory distress/dyspnea/respiratory failure/lung volume reduction and stillbirth/neonatal death. An important gene associated with Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease is PHOX2B (paired-like homeobox 2b), and among its related pathways are Neural Crest Differentiation and Transcription factors in neurogenesis. The compounds colchicine and propargylamine have been mentioned in the context of this disorder. Affiliated tissues include lung, and related mouse phenotypes are pigmentation and embryogenesis.

Description from OMIM:46 209880

Aliases & Classifications for Central Hypoventilation Syndrome, Congenital, with or Without...

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Sources:
46OMIM, 48Orphanet, 62UMLS, 26ICD10 via Orphanet, 63UMLS via Orphanet, 35MESH via Orphanet
See all sources

Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease, Aliases & Descriptions:

Name: Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease 46
Congenital Central Alveolar Hypoventilation Syndrome 48 62
Ondine-Hirschsprung Disease 48 62
Haddad Syndrome 48 62
Ondine Syndrome 48 62
Cchs 48 62
 
Congenital Central Alveolar Hypoventilation - Hirschsprung Disease 48
Central Congenital Hypoventilation Syndrome 48
Ondine-Hirschsprung Syndrome 48
Ondine's Curse 62
Ondine Curse 48


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Fetal diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

48
congenital central alveolar hypoventilation syndrome:
Inheritance: Autosomal dominant,Sporadic; Age of onset: Neonatal/infancy; Age of death: Normal
ondine-hirschsprung disease:
Inheritance: Autosomal dominant,Multigenic/multifactorial; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


External Ids:

ICD10 via Orphanet26 G47.3
UMLS via Orphanet63 C1275808, C1859587
OMIM46 209880
MESH via Orphanet35 C536209

Related Diseases for Central Hypoventilation Syndrome, Congenital, with or Without...

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Diseases related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 45)
idRelated DiseaseScoreTop Affiliating Genes
1central hypoventilation syndrome31.2GDNF
2hirschsprung's disease29.6PHOX2B, RET, EDN3, GDNF
3peritoneal carcinoma10.4BRCA1
4anterior spinal artery syndrome10.3
5familial medullary thyroid carcinoma10.3GDNF
621-hydroxylase deficiency10.3
7neuroblastoma10.3PHOX2B, BDNF
8familial colorectal cancer10.2BRCA1, RET
9autosomal dominant disease10.2BRCA1, RET
10cowden disease10.2RET, BRCA1
11waardenburg syndrome type 410.2RET, EDN3
12developmental disabilities10.2RET, BDNF
13waardenburg's syndrome10.2EDN3, RET
14carcinoid syndrome10.1RET, ASCL1
15congenital central hypoventilation syndrome10.1
16renal dysplasia10.1GDNF, RET
17neuroma10.1GDNF, RET
18multiple endocrine neoplasia type 2a10.1RET, GDNF
19renal agenesis10.1RET, GDNF
20multiple endocrine neoplasia10.1GDNF, RET
21neurofibromatosis10.1RET, GDNF
22nodular hidradenoma10.0
23clear cell hidradenoma10.0
24sudden infant death syndrome10.0
25hidradenoma10.0
26rohhad10.0
27brain ischemia10.0BDNF, GDNF
28motor neuron disease10.0GDNF, BDNF
29pancreatic cancer10.0GDNF, RET
30teratocarcinoma10.0GDNF, ASCL1
31temporal lobe epilepsy10.0GDNF, BDNF
32toxic encephalopathy10.0BDNF, GDNF
33stroke, ischemic10.0BDNF, GDNF
34mood disorder10.0GDNF, BDNF
35prion disease9.9BDNF, GDNF
36pituitary adenoma9.9GDNF, RET
37huntington's disease9.9BDNF, GDNF
38thyroid medullary carcinoma9.9RET, ASCL1, GDNF
39neuroendocrine tumor9.9RET, ASCL1, GDNF
40bipolar disorder9.9BDNF, GDNF
41intestinal obstruction9.8RET, EDN3, GDNF
42wilms tumor9.8GDNF, BDNF
43parkinson's disease9.8BDNF, GDNF
44pheochromocytoma9.6ASCL1, GDNF, EDN3, RET
45adenoma9.4ASCL1, GDNF, BRCA1, EDN3, RET

Graphical network of the top 20 diseases related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease:



Diseases related to central hypoventilation syndrome, congenital, with or without hirschsprung disease

Symptoms for Central Hypoventilation Syndrome, Congenital, with or Without...

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Symptoms by clinical synopsis from OMIM:

209880

Clinical features from OMIM:

209880

Symptoms:

48 (show all 21)
  • dolichocolon/megacolon/megadolichocolon/hirschsprung's disease
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • stillbirth/neonatal death
  • hypotonia
  • seizures/epilepsy/absences/spasms/status epilepticus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • central nervous system/peripheral nerves neoplasm/tumor/carcinoma/cancer
  • strabismus/squint
  • respiratory rhythm disorder
  • apnea/sleep apnea
  • dysautonomia/autonomous nervous sytem anomalies
  • autosomal dominant inheritance
  • short stature/dwarfism/nanism
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • death in infancy
  • sensorineural deafness/hearing loss
  • neuroblastoma
  • oligoamnios
  • polyhydramnios
  • fetal immobility/abnormal fetal movements

HPO human phenotypes related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease:

(show all 33)
id Description Frequency HPO Source Accession
1 respiratory insufficiency hallmark (90%) HP:0002093
2 aganglionic megacolon hallmark (90%) HP:0002251
3 strabismus hallmark (90%) HP:0000486
4 respiratory insufficiency hallmark (90%) HP:0002093
5 apnea hallmark (90%) HP:0002104
6 aganglionic megacolon hallmark (90%) HP:0002251
7 short stature hallmark (90%) HP:0004322
8 seizures typical (50%) HP:0001250
9 muscular hypotonia typical (50%) HP:0001252
10 cognitive impairment typical (50%) HP:0100543
11 seizures occasional (7.5%) HP:0001250
12 muscular hypotonia occasional (7.5%) HP:0001252
13 neoplasm of the nervous system occasional (7.5%) HP:0004375
14 cognitive impairment occasional (7.5%) HP:0100543
15 sensorineural hearing impairment occasional (7.5%) HP:0000407
16 prenatal movement abnormality occasional (7.5%) HP:0001557
17 polyhydramnios occasional (7.5%) HP:0001561
18 oligohydramnios occasional (7.5%) HP:0001562
19 neuroblastoma occasional (7.5%) HP:0003006
20 autosomal dominant inheritance HP:0000006
21 abnormality of the mouth HP:0000153
22 posteriorly rotated ears HP:0000358
23 low-set ears HP:0000369
24 downslanted palpebral fissures HP:0000494
25 hyperhidrosis HP:0000975
26 abnormality of the cardiovascular system HP:0001626
27 constipation HP:0002019
28 aganglionic megacolon HP:0002251
29 hypoventilation HP:0002791
30 ganglioneuroma HP:0003005
31 abnormality of temperature regulation HP:0004370
32 ganglioneuroblastoma HP:0006747
33 feeding difficulties HP:0011968

Drugs & Therapeutics for Central Hypoventilation Syndrome, Congenital, with or Without...

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Drug clinical trials:

Search ClinicalTrials for Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease

Search NIH Clinical Center for Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease

Genetic Tests for Central Hypoventilation Syndrome, Congenital, with or Without...

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Anatomical Context for Central Hypoventilation Syndrome, Congenital, with or Without...

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MalaCards organs/tissues related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease:

32
Lung

Animal Models for Central Hypoventilation Syndrome, Congenital, with or Without... or affiliated genes

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MGI Mouse Phenotypes related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease:

36 (show all 14)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00011869.0ASCL1, EDN3, BRCA1
2MP:00053808.4RET, BRCA1, PHOX2B, EDN3
3MP:00053888.4BDNF, PHOX2B, RET, ASCL1, BRCA1
4MP:00107718.4BRCA1, EDN3, ASCL1, BDNF
5MP:00053858.3PHOX2B, GDNF, BRCA1, RET
6MP:00028738.3RET, ASCL1, PHOX2B, BDNF, BRCA1
7MP:00053798.3RET, ASCL1, BRCA1, GDNF
8MP:00053897.9GDNF, RET, BDNF, BRCA1
9MP:00053817.8GDNF, EDN3, BRCA1, RET, BDNF
10MP:00053847.6PHOX2B, BRCA1, BDNF, RET, ASCL1, GDNF
11MP:00053787.5RET, GDNF, ASCL1, PHOX2B, BRCA1, BDNF
12MP:00053867.0BRCA1, EDN3, ASCL1, RET, PHOX2B, BDNF
13MP:00036317.0BRCA1, EDN3, ASCL1, RET, PHOX2B, BDNF
14MP:00107687.0BRCA1, GDNF, EDN3, ASCL1, RET, PHOX2B

Publications for Central Hypoventilation Syndrome, Congenital, with or Without...

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Variations for Central Hypoventilation Syndrome, Congenital, with or Without...

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UniProtKB/Swiss-Prot genetic disease variations for Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease:

64
id Symbol AA change Variation ID SNP ID
1BDNFp.Thr2IleVAR_018260rs8192466
2PHOX2Bp.Arg141GlnVAR_046900
3PHOX2Bp.Gln143ArgVAR_046901
4RETp.Arg67HisVAR_018153rs192489011
5RETp.Arg114HisVAR_018154
6RETp.Ala432GluVAR_018155
7RETp.Pro1039LeuVAR_018157rs79853121

Clinvar genetic disease variations for Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease:

6
id Gene Name Type Significance SNP ID Assembly Location
1RETNM_020975.4(RET): c.341G> A (p.Arg114His)single nucleotide variantPathogenicrs76397662GRCh37Chr 10, 43597793: 43597793
2EDN3EDN3, 1-BP INSinsertionPathogenic
3NM_170731.4(BDNF): c.29C> T (p.Thr10Ile)single nucleotide variantPathogenicrs8192466GRCh37Chr 11, 27680107: 27680107
4ASCL1NM_004316.3(ASCL1): c.52C> A (p.Pro18Thr)single nucleotide variantPathogenicrs267606667GRCh37Chr 12, 103352074: 103352074
5ASCL1ASCL1, 15-BP DEL, NT111deletionPathogenic
6PHOX2BLRG_513p1: p.Ala260(5_9)NT expansionPathogenic
7PHOX2BNM_003924.3(PHOX2B): c.618dupC (p.Ser207Glnfs)duplicationPathogenicGRCh37Chr 4, 41748151: 41748151
8PHOX2BPHOX2B, 37-BP DEL, NT722deletionPathogenic
9GDNFNM_000514.3(GDNF): c.277C> T (p.Arg93Trp)single nucleotide variantPathogenicrs36119840GRCh37Chr 5, 37816112: 37816112

Expression for genes affiliated with Central Hypoventilation Syndrome, Congenital, with or Without...

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Expression patterns in normal tissues for genes affiliated with Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease

Search GEO for disease gene expression data for Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease.

Pathways for genes affiliated with Central Hypoventilation Syndrome, Congenital, with or Without...

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Pathways related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.6PHOX2B, ASCL1
29.6PHOX2B, ASCL1
39.2GDNF, RET
49.2RET, GDNF
59.1BDNF, GDNF
6
Show member pathways
Development ERBB family signaling60
Development GDNF family signaling60
8.7GDNF, RET, BDNF
78.7ASCL1, RET, PHOX2B, BDNF

Compounds for genes affiliated with Central Hypoventilation Syndrome, Congenital, with or Without...

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Compounds related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease according to GeneCards/GeneDecks:

(show all 49)
idCompoundScoreTop Affiliating Genes
1colchicine44 61 2 28 1113.5BDNF, BRCA1
2propargylamine449.5GDNF, BDNF
3riluzole44 28 1111.5BDNF, GDNF
4dopac449.5BDNF, GDNF
5tetrodotoxin44 61 2811.5BDNF, EDN3
6rasagiline44 1110.5GDNF, BDNF
71 methyl 4 phenylpyridinium449.5BDNF, GDNF
8selegiline44 1110.5GDNF, BDNF
9phenylalanine449.5ASCL1, RET, BDNF
10agar449.4BRCA1, RET, BDNF
116-hydroxydopamine449.4BDNF, GDNF
12mptp449.4BDNF, GDNF
13nocodazole44 1110.3BRCA1, BDNF
14guanylate449.3BRCA1, EDN3
15capsaicin44 2810.3BDNF, GDNF
16melatonin44 28 61 24 1113.2GDNF, BDNF
17catecholamine449.1BDNF, RET, GDNF
18choline44 24 1111.1GDNF, RET, BDNF
19hydrogen44 2410.1BDNF, BRCA1, EDN3
20pd 98,059449.1GDNF, RET, BDNF
21ly294002449.1BDNF, RET, GDNF
22wortmannin449.0BDNF, RET, GDNF
23thymidine44 2410.0EDN3, BRCA1, BDNF
24genistein44 28 61 2 24 1114.0GDNF, BRCA1, RET
25dbc-amp448.9BDNF, EDN3, GDNF
26levodopa44 119.9GDNF, EDN3, BDNF
27acetylcholine44 50 28 24 1112.9BDNF, EDN3, GDNF
28methionine448.8BDNF, RET, BRCA1, EDN3
29kainate44 289.8BDNF, GDNF
30potassium44 24 1110.8GDNF, EDN3, BDNF
31phosphoinositide448.8BDNF, EDN3, GDNF
32testosterone44 61 24 1111.8BDNF, RET, BRCA1, EDN3
33lysine448.8EDN3, BRCA1, ASCL1, BDNF
34adenylate448.7GDNF, EDN3, BDNF
35h2o2448.6BDNF, BRCA1, GDNF
36norepinephrine44 24 1110.6GDNF, EDN3, PHOX2B, BDNF
37aspartate448.5BDNF, RET, EDN3, GDNF
38lipid448.5BDNF, RET, BRCA1, GDNF
39oligonucleotide448.5GDNF, EDN3, BRCA1, RET
40retinoic acid44 249.2BDNF, RET, ASCL1, BRCA1, GDNF
41cyclic amp44 249.2GDNF, EDN3, RET, PHOX2B, BDNF
42alanine448.2GDNF, EDN3, BRCA1, RET, PHOX2B
43vegf448.0GDNF, EDN3, BRCA1, RET, BDNF
44phosphatidylinositol448.0BDNF, RET, BRCA1, EDN3, GDNF
45atp44 289.0GDNF, EDN3, BRCA1, RET, BDNF
46serine448.0GDNF, EDN3, BRCA1, RET, BDNF
47calcium44 50 24 1110.9GDNF, EDN3, BRCA1, RET, BDNF
48dopamine44 28 24 1110.7BDNF, PHOX2B, RET, ASCL1, EDN3, GDNF
49tyrosine447.2GDNF, EDN3, BRCA1, ASCL1, RET, PHOX2B

GO Terms for genes affiliated with Central Hypoventilation Syndrome, Congenital, with or Without...

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Biological processes related to Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease according to GeneCards/GeneDecks:

(show all 13)
idNameGO IDScoreTop Affiliating Genes
1noradrenergic neuron developmentGO:0033589.9PHOX2B, ASCL1
2sympathetic ganglion developmentGO:0615499.8PHOX2B, ASCL1
3ureteric bud developmentGO:0016579.7BDNF, RET
4negative regulation of neuron differentiationGO:0456659.6ASCL1, PHOX2B
5inner ear developmentGO:0488399.6PHOX2B, BDNF
6regulation of gene expressionGO:0104689.5PHOX2B, ASCL1
7neuron migrationGO:0017649.3ASCL1, PHOX2B
8positive regulation of neuron differentiationGO:0456669.3ASCL1, PHOX2B, BDNF
9enteric nervous system developmentGO:0484849.1RET, GDNF, PHOX2B
10negative regulation of neuron apoptotic processGO:0435249.1BDNF, GDNF
11sympathetic nervous system developmentGO:0484859.1PHOX2B, ASCL1, GDNF
12neural crest cell migrationGO:0017558.9GDNF, EDN3, RET
13positive regulation of transcription from RNA polymerase II promoterGO:0459448.5PHOX2B, ASCL1, BRCA1, GDNF

Products for genes affiliated with Central Hypoventilation Syndrome, Congenital, with or Without...

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Sources for Central Hypoventilation Syndrome, Congenital, with or Without...

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet