MCID: CNT097
MIFTS: 65

Central Hypoventilation Syndrome, Congenital malady

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

Summaries for Central Hypoventilation Syndrome, Congenital

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OMIM:47 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, also known as central congenital hypoventilation syndrome, is related to sudden infant death syndrome and neuroblastoma, and has symptoms including respiratory insufficiency, aganglionic megacolon and strabismus. An important gene associated with Central Hypoventilation Syndrome, Congenital is PHOX2B (paired-like homeobox 2b), and among its related pathways are Transcription factors in neurogenesis and Amphetamine addiction. The compounds 3-nitropropionic acid and bq 3020 have been mentioned in the context of this disorder. Affiliated tissues include lung, eye and heart, and related mouse phenotypes are pigmentation and no phenotypic analysis.

Genetics Home Reference:23 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.

NIH Rare Diseases:43 Congenital central hypoventilation syndrome (cchs) is a disorder of the autonomic nervous system that causes individuals to hypoventilate (especially during sleep), resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. symptoms usually begin shortly after birth; affected infants hypoventilate upon falling asleep and exhibit a bluish appearance of the skin or lips (cyanosis). other features may include difficulty regulating heart rate and blood pressure; decreased perception of pain; low body temperature; occasional episodes of profuse sweating; hirschsprung disease; learning difficulties; eye abnormalities; and a characteristic appearance with a short, wide, somewhat flattened face. it is caused by mutations in the phox2b gene and is inherited in an autosomal dominant manner, but over 90 percent of cases result from new mutations and occur in people with no history of the disorder in their family. treatment typically includes mechanical ventilation or use of a diaphragm pacemaker. last updated: 5/28/2012

GeneReviews summary for ondine

Aliases & Classifications for Central Hypoventilation Syndrome, Congenital

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Sources:
47OMIM, 11diseasecard, 21GeneReviews, 43NIH Rare Diseases, 22GeneTests, 23Genetics Home Reference, 45Novoseek, 49Orphanet, 24GTR, 28ICD10 via Orphanet, 63UMLS via Orphanet, 36MESH via Orphanet
See all sources

Central Hypoventilation Syndrome, Congenital, Aliases & Descriptions:

Name: Central Hypoventilation Syndrome, Congenital 47 45
Central Congenital Hypoventilation Syndrome 43 22 49
Congenital Central Hypoventilation Syndrome 21 43 23
Ondine Syndrome 43 23 49
Haddad Syndrome 47 23 49
Cchs 43 23 49
Congenital Central Alveolar Hypoventilation Syndrome 43 49
Congenital Failure of Autonomic Control 43 23
Congenital Central Hypoventilation 23 24
Central Hypoventilation Syndrome 47 11
 
Ondine-Hirschsprung Disease 23 49
Ondine Curse 43 49
Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease 47
Congenital Central Alveolar Hypoventilation - Hirschsprung Disease 49
Idiopathic Congenital Central Alveolar Hypoventilation 43
Primary Alveolar Hypoventilation 43
Ondine-Hirschsprung Syndrome 49
Congenital Ondine Curse 43
Ondine's Curse 43


Classifications:

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


Characteristics (Orphanet epidemiological data):

49
central congenital hypoventilation syndrome:
Inheritance: Autosomal dominant,Not applicable; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy
haddad syndrome:
Inheritance: Autosomal dominant,Multigenic/multifactorial; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal


External Ids:

OMIM47 209880
Orphanet49 661, 99803
ICD10 via Orphanet28 G47.3
UMLS via Orphanet63 C1275808, C1859587
MESH via Orphanet36 C536209

Related Diseases for Central Hypoventilation Syndrome, Congenital

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Diseases related to Central Hypoventilation Syndrome, Congenital via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 75)
idRelated DiseaseScoreTop Affiliating Genes
1sudden infant death syndrome30.7TH, PHOX2B
2neuroblastoma30.4TH, PHOX2B, BDNF
3ganglioneuroma30.2RET, TH
4pulmonary hypertension30.2EDN3, EDNRB
5hirschsprung disease 130.2GDNF, PHOX2B, RET, EDN3, EDNRB
6cerebritis10.4
7sleep apnea10.4
8anterior spinal artery syndrome10.3
9western equine encephalitis10.2
10hypersomnia10.2
11obstructive sleep apnea10.2
12central sleep apnea10.2
13neuronitis10.2
14hyperinsulinism10.2
15down syndrome10.2
16encephalitis10.2
17esophagitis10.2
18ganglioneuroblastoma10.2
19hyperglycemia10.2
20hyperthyroidism10.2
21influenza10.2
22learning disability10.2
23meningitis10.2
24haemophilus influenzae10.2
25rohhad10.2
26autonomic dysfunction10.2
27hypoxia10.2
28cor pulmonale10.2
29hemimegalencephaly10.1
30medullary thyroid carcinoma, familial10.0GDNF
31clear cell hidradenoma10.0
32nodular hidradenoma10.0
33hidradenoma10.0
34renal dysplasia10.0RET, GDNF
35neuroma10.0GDNF, RET
36multiple endocrine neoplasia iia10.0RET, GDNF
37renal hypodysplasia/aplasia 110.0GDNF, RET
38neurofibromatosis10.0GDNF, RET
39brain ischemia10.0GDNF, BDNF
40motor neuron disease10.0GDNF, BDNF
41temporal lobe epilepsy10.0BDNF, GDNF
42neuroendocrine tumor10.0GDNF, RET, ASCL1
43neonatal hypoxic and ischemic brain injury10.0TH, BDNF
44bipolar disorder10.0TH, BDNF
45pancreatic cancer10.0RET, GDNF
46rett syndrome10.0TH, BDNF
47waardenburg syndrome type 410.0EDN3, EDNRB, RET
48waardenburg's syndrome10.0EDNRB, EDN3, RET
49paraganglioma10.0RET, TH
50multiple system atrophy10.0TH, GDNF

Graphical network of the top 20 diseases related to Central Hypoventilation Syndrome, Congenital:



Diseases related to central hypoventilation syndrome, congenital

Symptoms for Central Hypoventilation Syndrome, Congenital

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Symptoms by clinical synopsis from OMIM:

209880

Clinical features from OMIM:

209880

Symptoms:

 49 (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:

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

Drugs & Therapeutics for Central Hypoventilation Syndrome, Congenital

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Drug clinical trials:

Search ClinicalTrials for Central Hypoventilation Syndrome, Congenital

Search NIH Clinical Center for Central Hypoventilation Syndrome, Congenital

Genetic Tests for Central Hypoventilation Syndrome, Congenital

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Genetic tests related to Central Hypoventilation Syndrome, Congenital:

id Genetic test Affiliating Genes
1 Congenital Central Hypoventilation Syndrome22 PHOX2B
2 Congenital Central Hypoventilation24

Anatomical Context for Central Hypoventilation Syndrome, Congenital

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MalaCards organs/tissues related to Central Hypoventilation Syndrome, Congenital:

33
Lung, Eye, Heart, Skin

Animal Models for Central Hypoventilation Syndrome, Congenital or affiliated genes

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MGI Mouse Phenotypes related to Central Hypoventilation Syndrome, Congenital:

37 (show all 15)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00011868.9EDNRB, EDN3, ASCL1
2MP:00030128.5TH, ASCL1, RET, BDNF
3MP:00053808.4PHOX2B, RET, EDN3, EDNRB
4MP:00028738.4TH, ASCL1, RET, PHOX2B, BDNF
5MP:00053798.2GDNF, TH, ASCL1, RET
6MP:00053918.1EDNRB, TH, ASCL1, PHOX2B, BDNF
7MP:00107718.0BDNF, ASCL1, TH, EDN3, EDNRB
8MP:00053817.8GDNF, EDNRB, EDN3, RET, BDNF
9MP:00053857.8GDNF, EDNRB, TH, RET, PHOX2B
10MP:00053887.7EDNRB, TH, ASCL1, RET, PHOX2B, BDNF
11MP:00053847.1GDNF, EDNRB, TH, ASCL1, RET, PHOX2B
12MP:00053787.0GDNF, EDNRB, TH, ASCL1, RET, PHOX2B
13MP:00053866.7BDNF, GDNF, EDNRB, EDN3, TH, ASCL1
14MP:00036316.7GDNF, EDNRB, EDN3, TH, ASCL1, RET
15MP:00107686.7GDNF, EDNRB, EDN3, TH, ASCL1, RET

Publications for Central Hypoventilation Syndrome, Congenital

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Variations for Central Hypoventilation Syndrome, Congenital

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UniProtKB/Swiss-Prot genetic disease variations for Central Hypoventilation Syndrome, Congenital:

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:

7
id Gene Variation 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

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Search GEO for disease gene expression data for Central Hypoventilation Syndrome, Congenital.

Pathways for genes affiliated with Central Hypoventilation Syndrome, Congenital

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Pathways related to Central Hypoventilation Syndrome, Congenital according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.8ASCL1, PHOX2B
2
Show member pathways
9.4TH, BDNF
39.4GDNF, RET
49.4GDNF, RET
59.2EDN3, EDNRB
6
Show member pathways
Development ERBB family signaling60
Development GDNF family signaling60
8.9BDNF, RET, GDNF
78.3RET, TH, ASCL1, BDNF, PHOX2B

Compounds for genes affiliated with Central Hypoventilation Syndrome, Congenital

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Compounds related to Central Hypoventilation Syndrome, Congenital according to GeneCards/GeneDecks:

(show top 50)    (show all 85)
idCompoundScoreTop Affiliating Genes
13-nitropropionic acid459.7BDNF, TH
2bq 302045 3010.6EDN3, EDNRB
3pd 142893459.6EDNRB, EDN3
4bq610459.6EDNRB, EDN3
5propargylamine459.6BDNF, GDNF
6fr13931745 3010.6EDN3, EDNRB
7tezosentan459.6EDN3, EDNRB
8sarafotoxin459.6EDN3, EDNRB
9irl 162045 3010.6EDN3, EDNRB
10bq78845 3010.6EDN3, EDNRB
11riluzole45 30 1311.5GDNF, BDNF
12bq12345 3010.5EDNRB, EDN3
13bosentan45 1310.4EDN3, EDNRB
14mhpg459.4TH, BDNF
15tetrodotoxin45 61 3011.4EDN3, TH, BDNF
16dbc-amp459.3BDNF, GDNF, EDN3
17carbachol45 30 1311.2EDN3, TH, BDNF
18dopac459.2BDNF, TH, GDNF
191 methyl 4 phenylpyridinium459.2TH, GDNF, BDNF
20selegiline45 1310.2BDNF, GDNF, TH
216-hydroxydopamine459.2TH, BDNF, GDNF
22mptp459.2BDNF, GDNF, TH
23kainate45 3010.1GDNF, TH, BDNF
24thapsigargin45 6110.1BDNF, EDN3, TH
25cocaine45 1310.0BDNF, TH, GDNF
26rasagiline45 1310.0BDNF, GDNF
27phenylalanine459.0ASCL1, BDNF, RET, TH
28levodopa45 139.8BDNF, GDNF, EDN3, TH
29melatonin45 30 61 26 1312.8GDNF, BDNF, EDNRB
30catecholamine458.8BDNF, TH, RET, GDNF
31choline45 26 1310.8GDNF, TH, BDNF, RET
32ly294002458.7GDNF, BDNF, TH, RET
33testosterone45 61 26 1311.7EDN3, RET, BDNF, TH
34lysine458.7EDNRB, EDN3, BDNF, ASCL1
35potassium45 26 1310.5EDNRB, BDNF, EDN3, GDNF
36h2o2458.1BDNF, EDNRB, GDNF, TH
37dexamethasone45 51 30 1311.1EDNRB, GDNF, EDN3, TH
38phosphatidylinositol458.0RET, EDN3, GDNF, BDNF, EDNRB
39cyclic amp45 269.0PHOX2B, RET, EDN3, BDNF, GDNF, TH
40acetylcholine45 51 30 26 1312.0BDNF, TH, EDN3, EDNRB, GDNF
41adenylate458.0EDNRB, BDNF, EDN3, GDNF, TH
42glutamate458.0EDNRB, GDNF, TH, BDNF, EDN3
43alanine457.7TH, EDNRB, EDN3, GDNF, PHOX2B, RET
44norepinephrine45 26 139.7TH, GDNF, EDNRB, EDN3, BDNF, PHOX2B
45dopamine45 30 26 1310.7GDNF, EDN3, TH, ASCL1, RET, PHOX2B
46retinoic acid45 268.6EDNRB, RET, BDNF, ASCL1, TH, GDNF
47aspartate457.6EDN3, EDNRB, GDNF, BDNF, TH, RET
48vegf457.6BDNF, RET, TH, EDN3, EDNRB, GDNF
49serine457.5GDNF, BDNF, RET, EDN3, EDNRB
50tyrosine456.8PHOX2B, ASCL1, BDNF, RET, TH, EDN3

GO Terms for genes affiliated with Central Hypoventilation Syndrome, Congenital

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Cellular components related to Central Hypoventilation Syndrome, Congenital according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1synaptic vesicleGO:00080219.4BDNF, TH

Biological processes related to Central Hypoventilation Syndrome, Congenital according to GeneCards/GeneDecks:

(show all 18)
idNameGO IDScoreTop Affiliating Genes
1noradrenergic neuron developmentGO:000335810.0ASCL1, PHOX2B
2sympathetic ganglion developmentGO:006154910.0PHOX2B, ASCL1
3inner ear developmentGO:00488399.7PHOX2B, BDNF
4negative regulation of neuron differentiationGO:00456659.7ASCL1, PHOX2B
5ureteric bud developmentGO:00016579.6RET, BDNF
6cerebral cortex developmentGO:00219879.6TH, ASCL1
7vein smooth muscle contractionGO:00148269.5EDNRB, EDN3
8positive regulation of neuron differentiationGO:00456669.5PHOX2B, ASCL1, BDNF
9posterior midgut developmentGO:00074979.5RET, EDNRB
10vasoconstrictionGO:00423109.5EDN3, EDNRB
11regulation of gene expressionGO:00104689.5ASCL1, PHOX2B
12sympathetic nervous system developmentGO:00484859.4ASCL1, PHOX2B, GDNF
13melanocyte differentiationGO:00303189.4EDNRB, EDN3
14response to painGO:00482659.4EDNRB, RET
15nervous system developmentGO:00073998.7BDNF, EDNRB, GDNF
16negative regulation of apoptotic processGO:00430668.7ASCL1, EDNRB, GDNF
17enteric nervous system developmentGO:00484848.6EDNRB, PHOX2B, RET, GDNF
18neural crest cell migrationGO:00017558.5GDNF, EDN3, EDNRB, RET

Products for genes affiliated with Central Hypoventilation Syndrome, Congenital

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Sources for Central Hypoventilation Syndrome, Congenital

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4CDC
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16FMA
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26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
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48OMIM via Orphanet
52PubMed
53QIAGEN
58SNOMED-CT via Orphanet
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63UMLS via Orphanet