MCID: CNT097
MIFTS: 58

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:45 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 congenital central alveolar 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: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.

NIH Rare Diseases:41 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:
45OMIM, 10diseasecard, 19GeneReviews, 41NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 43Novoseek, 47Orphanet, 22GTR, 60UMLS, 26ICD10 via Orphanet, 61UMLS via Orphanet, 34MESH via Orphanet
See all sources

Central Hypoventilation Syndrome, Congenital, Aliases & Descriptions:

Name: Central Hypoventilation Syndrome, Congenital 45 43
Congenital Central Alveolar Hypoventilation Syndrome 41 47 60
Central Congenital Hypoventilation Syndrome 41 20 47
Congenital Central Hypoventilation Syndrome 19 41 21
Congenital Central Hypoventilation 21 22 60
Haddad Syndrome 45 21 47
Ondine Syndrome 41 21 47
Cchs 41 21 47
Congenital Failure of Autonomic Control 41 21
Central Hypoventilation Syndrome 45 10
Ondine-Hirschsprung Disease 21 47
Ondine Curse 41 47
 
Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease 45
Congenital Central Alveolar Hypoventilation - Hirschsprung Disease 47
Idiopathic Congenital Central Alveolar Hypoventilation 41
Central Alveolar Hypoventilation Syndrome 60
Sleep-Related Respiratory Failure 60
Primary Alveolar Hypoventilation 41
Cchs with Hirschsprung Disease 60
Ondine-Hirschsprung Syndrome 47
Congenital Ondine Curse 41
Sleep Apnea, Central 60
Ondine's Curse 41


Classifications:

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


Characteristics (Orphanet epidemiological data):

47
congenital central alveolar 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:

OMIM45 209880
Orphanet47 661, 99803
ICD10 via Orphanet26 G47.3
UMLS via Orphanet61 C1275808, C1859587
MESH via Orphanet34 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 Suite gene sharing:

(show top 50)    (show all 76)
idRelated DiseaseScoreTop Affiliating Genes
1sudden infant death syndrome30.8TH, PHOX2B
2neuroblastoma30.3TH, PHOX2B, BDNF
3ganglioneuroma30.3RET, TH
4pulmonary hypertension30.3EDN3, EDNRB
5hirschsprung disease 129.7GDNF, EDNRB, EDN3, RET, PHOX2B
6medullary thyroid carcinoma, familial10.4GDNF
7cerebritis10.4
8sleep apnea10.4
9anterior spinal artery syndrome10.3
10western equine encephalitis10.2
11hypersomnia10.2
12renal dysplasia10.2RET, GDNF
13neuroma10.2RET, GDNF
14multiple endocrine neoplasia iia10.2RET, GDNF
15renal hypodysplasia/aplasia 110.2RET, GDNF
16obstructive sleep apnea10.2
17central sleep apnea10.2
18neuronitis10.2
19hyperinsulinism10.2
20down syndrome10.2
21encephalitis10.2
22esophagitis10.2
23ganglioneuroblastoma10.2
24hyperglycemia10.2
25hyperthyroidism10.2
26influenza10.2
27learning disability10.2
28meningitis10.2
29haemophilus influenzae10.2
30rohhad10.2
31autonomic dysfunction10.2
32hypoxia10.2
33cor pulmonale10.2
34neurofibromatosis10.2RET, GDNF
35hemimegalencephaly10.1
36brain ischemia10.1BDNF, GDNF
37temporal lobe epilepsy10.1GDNF, BDNF
38motor neuron disease10.1GDNF, BDNF
39neuroendocrine tumor10.1RET, ASCL1, GDNF
40neonatal hypoxic and ischemic brain injury10.1BDNF, TH
41neurotic disorder10.0BDNF, TH
42clear cell hidradenoma10.0
43nodular hidradenoma10.0
44hidradenoma10.0
45pancreatic cancer10.0RET, GDNF
46rett syndrome10.0BDNF, TH
47waardenburg syndrome type 410.0RET, EDN3, EDNRB
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:

 47 (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 Syndrome20 PHOX2B
2 Congenital Central Hypoventilation22

Anatomical Context for Central Hypoventilation Syndrome, Congenital

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

31
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:

35 (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:

62
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:

6
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 Suite gene sharing:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.4BDNF, TH
29.4RET, GDNF
39.4GDNF, RET
49.2EDN3, EDNRB
5
Show member pathways
Development ERBB family signaling58
Development GDNF family signaling58
8.9BDNF, RET, GDNF
68.3BDNF, PHOX2B, RET, ASCL1, TH

Compounds for genes affiliated with Central Hypoventilation Syndrome, Congenital

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Compounds related to Central Hypoventilation Syndrome, Congenital according to GeneCards Suite gene sharing:

(show top 50)    (show all 85)
idCompoundScoreTop Affiliating Genes
13-nitropropionic acid439.7BDNF, TH
2bq 302043 2810.6EDN3, EDNRB
3pd 142893439.6EDNRB, EDN3
4bq610439.6EDNRB, EDN3
5propargylamine439.6BDNF, GDNF
6fr13931743 2810.6EDN3, EDNRB
7tezosentan439.6EDN3, EDNRB
8sarafotoxin439.6EDN3, EDNRB
9irl 162043 2810.6EDN3, EDNRB
10bq78843 2810.6EDN3, EDNRB
11riluzole43 28 1211.5GDNF, BDNF
12bq12343 2810.5EDNRB, EDN3
13bosentan43 1210.4EDN3, EDNRB
14mhpg439.4TH, BDNF
15tetrodotoxin43 59 2811.4EDN3, TH, BDNF
16dbc-amp439.3BDNF, GDNF, EDN3
17carbachol43 28 1211.2EDN3, TH, BDNF
18dopac439.2BDNF, TH, GDNF
191 methyl 4 phenylpyridinium439.2TH, GDNF, BDNF
20selegiline43 1210.2BDNF, GDNF, TH
216-hydroxydopamine439.2TH, BDNF, GDNF
22mptp439.2BDNF, GDNF, TH
23kainate43 2810.1GDNF, TH, BDNF
24thapsigargin43 5910.1BDNF, EDN3, TH
25cocaine43 1210.0BDNF, TH, GDNF
26rasagiline43 1210.0BDNF, GDNF
27phenylalanine439.0ASCL1, BDNF, RET, TH
28levodopa43 129.8BDNF, GDNF, EDN3, TH
29melatonin43 28 59 24 1212.8GDNF, BDNF, EDNRB
30catecholamine438.8BDNF, TH, RET, GDNF
31choline43 24 1210.8GDNF, TH, BDNF, RET
32ly294002438.7GDNF, BDNF, TH, RET
33testosterone43 59 24 1211.7EDN3, RET, BDNF, TH
34lysine438.7EDNRB, EDN3, BDNF, ASCL1
35potassium43 24 1210.5EDNRB, BDNF, EDN3, GDNF
36h2o2438.1BDNF, EDNRB, GDNF, TH
37dexamethasone43 49 28 1211.1EDNRB, GDNF, EDN3, TH
38phosphatidylinositol438.0RET, EDN3, GDNF, BDNF, EDNRB
39cyclic amp43 249.0PHOX2B, RET, EDN3, BDNF, GDNF, TH
40acetylcholine43 49 28 24 1212.0BDNF, TH, EDN3, EDNRB, GDNF
41adenylate438.0EDNRB, BDNF, EDN3, GDNF, TH
42glutamate438.0EDNRB, GDNF, TH, BDNF, EDN3
43alanine437.7TH, EDNRB, EDN3, GDNF, PHOX2B, RET
44norepinephrine43 24 129.7TH, GDNF, EDNRB, EDN3, BDNF, PHOX2B
45dopamine43 28 24 1210.7GDNF, EDN3, TH, ASCL1, RET, PHOX2B
46retinoic acid43 248.6EDNRB, RET, BDNF, ASCL1, TH, GDNF
47aspartate437.6EDN3, EDNRB, GDNF, BDNF, TH, RET
48vegf437.6BDNF, RET, TH, EDN3, EDNRB, GDNF
49serine437.5GDNF, BDNF, RET, EDN3, EDNRB
50tyrosine436.8PHOX2B, 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 Suite gene sharing:

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

Biological processes related to Central Hypoventilation Syndrome, Congenital according to GeneCards Suite gene sharing:

(show all 18)
idNameGO IDScoreTop Affiliating Genes
1noradrenergic neuron developmentGO:000335810.0PHOX2B, ASCL1
2sympathetic ganglion developmentGO:006154910.0PHOX2B, ASCL1
3inner ear developmentGO:00488399.7PHOX2B, BDNF
4negative regulation of neuron differentiationGO:00456659.7PHOX2B, ASCL1
5ureteric bud developmentGO:00016579.6BDNF, RET
6cerebral cortex developmentGO:00219879.6TH, ASCL1
7vein smooth muscle contractionGO:00148269.5EDN3, EDNRB
8positive regulation of neuron differentiationGO:00456669.5ASCL1, PHOX2B, BDNF
9posterior midgut developmentGO:00074979.5EDNRB, RET
10regulation of gene expressionGO:00104689.5PHOX2B, ASCL1
11vasoconstrictionGO:00423109.4EDNRB, EDN3
12sympathetic nervous system developmentGO:00484859.4PHOX2B, ASCL1, GDNF
13melanocyte differentiationGO:00303189.4EDN3, EDNRB
14response to painGO:00482659.4EDNRB, RET
15nervous system developmentGO:00073998.7GDNF, EDNRB, BDNF
16negative regulation of apoptotic processGO:00430668.7ASCL1, EDNRB, GDNF
17enteric nervous system developmentGO:00484848.6PHOX2B, RET, EDNRB, GDNF
18neural crest cell migrationGO:00017558.5GDNF, EDNRB, EDN3, RET

Products for genes affiliated with Central Hypoventilation Syndrome, Congenital

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Sources for Central Hypoventilation Syndrome, Congenital

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3CDC
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24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet