CCHS
MCID: CNT091
MIFTS: 50

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

Genetic diseases, Neuronal diseases, Fetal diseases, Rare diseases categories

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

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OMIM:46 Idiopathic congenital central hypoventilation syndrome, also known as 'Ondine's curse' (Deonna et al., 1974), is a rare... (209880) more...

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 respiratory insufficiency, aganglionic megacolon and strabismus. 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 tetrodotoxin and propargylamine have been mentioned in the context of this disorder. Affiliated tissues include lung, and related mouse phenotypes are taste/olfaction and respiratory system.

Genetics Home Reference:22 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.

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

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Sources:
46OMIM, 48Orphanet, 61UMLS, 27ICD10 via Orphanet, 62UMLS 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 61
Ondine-Hirschsprung Disease 48 61
Haddad Syndrome 48 61
Ondine Syndrome 48 61
Cchs 48 61
 
Congenital Central Alveolar Hypoventilation - Hirschsprung Disease 48
Central Congenital Hypoventilation Syndrome 48
Ondine-Hirschsprung Syndrome 48
Ondine's Curse 61
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 Orphanet27 G47.3
UMLS via Orphanet62 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 42)
idRelated DiseaseScoreTop Affiliating Genes
1central hypoventilation syndrome31.2GDNF
2hirschsprung's disease29.5GDNF, PHOX2B, EDN3, RET
3anterior spinal artery syndrome10.3
4familial medullary thyroid carcinoma10.3GDNF
521-hydroxylase deficiency10.3
6neuroblastoma10.2BDNF, PHOX2B
7waardenburg syndrome type 410.2EDN3, RET
8developmental disabilities10.2RET, BDNF
9waardenburg's syndrome10.2EDN3, RET
10carcinoid syndrome10.1ASCL1, RET
11congenital central hypoventilation syndrome10.1
12renal dysplasia10.1GDNF, RET
13neuroma10.1GDNF, RET
14multiple endocrine neoplasia type 2a10.1RET, GDNF
15renal agenesis10.1GDNF, RET
16multiple endocrine neoplasia10.1RET, GDNF
17neurofibromatosis10.0GDNF, RET
18nodular hidradenoma10.0
19clear cell hidradenoma10.0
20sudden infant death syndrome10.0
21hidradenoma10.0
22rohhad10.0
23brain ischemia10.0BDNF, GDNF
24temporal lobe epilepsy10.0BDNF, GDNF
25motor neuron disease10.0BDNF, GDNF
26toxic encephalopathy10.0GDNF, BDNF
27pancreatic cancer10.0GDNF, RET
28stroke, ischemic10.0BDNF, GDNF
29teratocarcinoma10.0ASCL1, GDNF
30mood disorder10.0GDNF, BDNF
31prion disease10.0BDNF, GDNF
32pituitary adenoma9.9GDNF, RET
33huntington's disease9.9BDNF, GDNF
34wilms tumor9.9GDNF, BDNF
35amyotrophic lateral sclerosis type 149.9BDNF, GDNF
36thyroid medullary carcinoma9.9ASCL1, RET, GDNF
37neuroendocrine tumor9.9ASCL1, GDNF, RET
38parkinson's disease9.8GDNF, BDNF
39intestinal obstruction9.8RET, GDNF, EDN3
40bipolar disorder9.8GDNF, BDNF
41pheochromocytoma9.6GDNF, ASCL1, RET, EDN3
42adenoma9.6ASCL1, EDN3, GDNF, 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
  • 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
  • stillbirth/neonatal death
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • hypotonia
  • seizures/epilepsy/absences/spasms/status epilepticus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • death in infancy
  • central nervous system/peripheral nerves neoplasm/tumor/carcinoma/cancer
  • 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
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053949.4BDNF, ASCL1
2MP:00053888.6BDNF, PHOX2B, RET, ASCL1
3MP:00028738.3BDNF, PHOX2B, RET, ASCL1
4MP:00053818.1GDNF, EDN3, RET, BDNF
5MP:00053847.9GDNF, ASCL1, RET, PHOX2B, BDNF
6MP:00053787.6GDNF, ASCL1, RET, PHOX2B, BDNF
7MP:00053867.3BDNF, PHOX2B, RET, ASCL1, EDN3, GDNF
8MP:00036317.3GDNF, EDN3, ASCL1, RET, PHOX2B, BDNF
9MP:00107687.3GDNF, EDN3, ASCL1, RET, PHOX2B, BDNF

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:

63
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:

7
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 variantPathogenic, risk factorrs36119840GRCh37Chr 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
19.5PHOX2B, ASCL1
29.5PHOX2B, ASCL1
39.2GDNF, RET
49.2RET, GDNF
59.1BDNF, GDNF
6
Show member pathways
Development ERBB family signaling59
Development GDNF family signaling59
8.7GDNF, RET, BDNF
78.6ASCL1, 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 48)
idCompoundScoreTop Affiliating Genes
1tetrodotoxin44 60 2911.6BDNF, EDN3
2propargylamine449.6GDNF, BDNF
3riluzole44 29 1211.6BDNF, GDNF
4dopac449.5BDNF, GDNF
5rasagiline44 1210.5BDNF, GDNF
61 methyl 4 phenylpyridinium449.5BDNF, GDNF
7selegiline44 1210.5BDNF, GDNF
86-hydroxydopamine449.5GDNF, BDNF
9mptp449.5BDNF, GDNF
10nifedipine44 29 50 1212.4BDNF, EDN3
11capsaicin44 2910.4GDNF, BDNF
12melatonin44 29 60 25 1213.4BDNF, GDNF
13phenylalanine449.4BDNF, RET, ASCL1
14kainate44 2910.4BDNF, GDNF
15methionine449.3EDN3, RET, BDNF
16carbachol44 29 1211.2BDNF, EDN3
17heparan sulfate44 2510.2RET, GDNF
18cocaine44 1210.2GDNF, BDNF
19lysine449.1BDNF, ASCL1, EDN3
20testosterone44 60 25 1212.1BDNF, RET, EDN3
21bromodeoxyuridine449.1BDNF, GDNF
22catecholamine449.1BDNF, RET, GDNF
23choline44 25 1211.1BDNF, RET, GDNF
24pd 98,059449.0BDNF, RET, GDNF
25ly294002449.0GDNF, RET, BDNF
26inositol 1,4,5 trisphosphate449.0BDNF, EDN3
27wortmannin449.0BDNF, RET, GDNF
28dbc-amp448.9BDNF, EDN3, GDNF
29levodopa44 129.9GDNF, EDN3, BDNF
30acetylcholine44 50 29 25 1212.9GDNF, EDN3, BDNF
31potassium44 25 1210.9BDNF, EDN3, GDNF
32phosphoinositide448.9GDNF, EDN3, BDNF
33oligonucleotide448.8GDNF, EDN3, RET
34adenylate448.8BDNF, EDN3, GDNF
35zinc44 259.7BDNF, EDN3, GDNF
36glutamate448.7BDNF, EDN3, GDNF
37alanine448.6GDNF, EDN3, RET, PHOX2B
38retinoic acid44 259.5GDNF, ASCL1, RET, BDNF
39norepinephrine44 25 1210.5GDNF, EDN3, PHOX2B, BDNF
40aspartate448.5GDNF, EDN3, RET, BDNF
41vegf448.5GDNF, EDN3, RET, BDNF
42phosphatidylinositol448.5GDNF, EDN3, RET, BDNF
43atp44 299.4BDNF, RET, EDN3, GDNF
44serine448.4GDNF, EDN3, RET, BDNF
45calcium44 50 25 1211.2GDNF, EDN3, RET, BDNF
46cyclic amp44 259.1GDNF, EDN3, RET, PHOX2B, BDNF
47dopamine44 29 25 1210.6BDNF, PHOX2B, RET, ASCL1, EDN3, GDNF
48tyrosine447.6GDNF, EDN3, ASCL1, RET, PHOX2B, BDNF

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 14)
idNameGO IDScoreTop Affiliating Genes
1noradrenergic neuron developmentGO:0033589.8PHOX2B, ASCL1
2sympathetic ganglion developmentGO:0615499.7PHOX2B, ASCL1
3inner ear developmentGO:0488399.7BDNF, PHOX2B
4ureteric bud developmentGO:0016579.7RET, BDNF
5negative regulation of neuron differentiationGO:0456659.7PHOX2B, ASCL1
6regulation of gene expressionGO:0104689.6PHOX2B, ASCL1
7neuron migrationGO:0017649.5ASCL1, PHOX2B
8positive regulation of neuron differentiationGO:0456669.2BDNF, PHOX2B, ASCL1
9enteric nervous system developmentGO:0484849.1PHOX2B, RET, GDNF
10sympathetic nervous system developmentGO:0484859.0PHOX2B, ASCL1, GDNF
11negative regulation of neuron apoptotic processGO:0435248.8BDNF, GDNF
12neural crest cell migrationGO:0017558.8GDNF, EDN3, RET
13positive regulation of transcription from RNA polymerase II promoterGO:0459448.6PHOX2B, ASCL1, GDNF
14signal transductionGO:0071658.6RET, EDN3, GDNF

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

idNameGO IDScoreTop Affiliating Genes
1growth factor activityGO:0080839.1BDNF, GDNF

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

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57SNOMED-CT via Orphanet
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