MCID: CNT097
MIFTS: 64

Central Hypoventilation Syndrome, Congenital

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Gastrointestinal diseases

Aliases & Classifications for Central Hypoventilation Syndrome, Congenital

MalaCards integrated aliases for Central Hypoventilation Syndrome, Congenital:

Name: Central Hypoventilation Syndrome, Congenital 57 75 55
Congenital Central Hypoventilation Syndrome 12 76 24 53 25 75 37 15
Cchs 57 12 76 53 25 59 75
Haddad Syndrome 57 25 59 29 6
Congenital Central Hypoventilation 25 29 6 73
Congenital Central Alveolar Hypoventilation Syndrome 12 59 73
Congenital Failure of Autonomic Control 53 25 75
Ondine Syndrome 12 25 59
Ondine Curse 12 59 75
Central Congenital Hypoventilation Syndrome 12 59
Central Hypoventilation Syndrome 57 13
Ondine-Hirschsprung Disease 25 59
Central Hypoventilation 29 6
Hypoventilation 44 73
Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease 57
Congenital Central Alveolar Hypoventilation-Hirschsprung Disease Syndrome 59
Idiopathic Congenital Central Alveolar Hypoventilation 53
Syndrome, Hypoventilation, Central, Congenital 40
Primary Alveolar Hypoventilation Syndrome 37
Central Alveolar Hypoventilation Syndrome 73
Autonomic Control, Congenital Failure of 57
Sleep-Related Respiratory Failure 73
Primary Alveolar Hypoventilation 53
Cchs with Hirschsprung Disease 73
Ondine-Hirschsprung Syndrome 59
Ondine Curse, Congenital 57
Congenital Ondine Curse 53
Sleep Apnea, Central 73
Ondine's Curse 76

Characteristics:

Orphanet epidemiological data:

59
ondine 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;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset usually at birth
worsening of symptoms during sleep
some patients have later onset of the disorder as young adults
patients often have other clinical symptoms resulting from dysfunction of the autonomic nervous system
hypoventilation occurs in the absence of primary neuromuscular, lung, or cardiac disease, or an identifiable brainstem lesion
most cases are caused by mutation in the phox2b gene


HPO:

32
central hypoventilation syndrome, congenital:
Mortality/Aging death in infancy
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Penetrance for the phox2b polyalanine repeat expansion mutation appears to be high. amiel et al [2003], sasaki et al [2003], weese-mayer et al [2003], matera et al [2004], and berry-kravis et al [2006] found no controls with a phox2b polyalanine repeat expansion mutation...

Classifications:



Summaries for Central Hypoventilation Syndrome, Congenital

NIH Rare Diseases : 53 Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system that affects breathing. It causes a person to hypoventilate (especially during sleep), resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. It have two forms of presentation, a classic form that usually begin shortly after birth in newborns, and a milder later-onset presentaition in toddlers, children and adults. 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; sporadic profuse sweating; Hirschsprung disease; constipation; learning difficulties; eye abnormalities; and a characteristic facial appearance (having a short, wide, somewhat flattened face). They can also have tumors of neural crest origin, such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. The later-onset  form is milder, and some cases may present as infants and children who die suddenly and unexpectedly (“SIDS” and “sudden unexplained death of childhood [SUDC]”).  CCHS is caused by a variation (mutation) in the PHOX2B gene and is inherited in an autosomal dominant manner. However, over 90% of cases are due to a new mutation in the affected person and are not inherited from a parent. Diagnosis is made with the clinical symptoms and the genetic test showing the variation in the PHOX2B gene. Treatment typically includes mechanical ventilation or use of a diaphragm pacemaker. People who have been diagnosed as newborns and adequately ventilated throughout childhood may reach the age of 20 to 30 years, and can live independently.  In the later-onset form, people who were diagnosed when they were 20 years or older have now reached the age of 30 to 55 years.

MalaCards based summary : Central Hypoventilation Syndrome, Congenital, also known as congenital central hypoventilation syndrome, is related to hirschsprung disease 1 and sudden infant death syndrome, and has symptoms including apnea, constipation and increased sweating. An important gene associated with Central Hypoventilation Syndrome, Congenital is PHOX2B (Paired Like Homeobox 2b), and among its related pathways/superpathways are MAPK signaling pathway and Neurotrophin signaling pathway. The drugs Desogestrel and Progestins have been mentioned in the context of this disorder. Affiliated tissues include lung, heart and brain, and related phenotypes are intellectual disability and seizures

OMIM : 57 Idiopathic congenital central hypoventilation syndrome, also known as 'Ondine's curse' (Deonna et al., 1974), is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular, lung or cardiac disease, or an identifiable brainstem lesion. Patients breathe normally while awake, but hypoventilate with normal respiratory rates and shallow breathing during sleep; more severely affected patients hypoventilate both awake and asleep. These patients typically present in the first hours of life with cyanosis and increased carbon dioxide during sleep. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia (reviewed by Weese-Mayer et al., 1999). Congenital central hypoventilation syndrome has been associated with several disorders classified as neurocristopathies, that is, aberrant phenotypes arising from a defect of migration or differentiation of neural crest cells. These include neuroblastoma (Haddad et al., 1978), ganglioneuroma (Swaminathan et al., 1989), and most frequently Hirschsprung disease (HSCR) which appears in 16% of CCHS patients. The association of CCHS and HSCR is referred to as Haddad syndrome. Congenital central hypoventilation can be a feature of other developmental disorders, such as those caused by mutation in the MECP2 gene (300005). (209880)

UniProtKB/Swiss-Prot : 75 Congenital central hypoventilation syndrome: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.

Genetics Home Reference : 25 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.

Disease Ontology : 12 An autonomic nervous system disease characterized by reduced responsiveness of the respiratory center to carbon dioxide, diminished pupillary light responses, and other symptoms related to defects in the autonomic nervous system and that has material basis in most commonly heterozygous mutation in the PHOX2B gene on chromosome 4p13 and less frequently mutations in the RET, GDNF, EDN3, BDNF, or ASCL1 genes.

Wikipedia : 76 Central hypoventilation syndrome (CHS) is a respiratory disorder that results in respiratory arrest... more...

GeneReviews: NBK1427

Related Diseases for Central Hypoventilation Syndrome, Congenital

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

(show all 44)
# Related Disease Score Top Affiliating Genes
1 hirschsprung disease 1 30.0 EDN3 EDNRB GDNF PHOX2B RET
2 sudden infant death syndrome 29.3 ASCL1 BDNF PHOX2A PHOX2B TH TLX3
3 obesity-hypoventilation syndrome 12.4
4 rapid-onset childhood obesity-hypothalamic dysfunction-hypoventilation-autonomic dysregulation syndrome 12.1
5 perry syndrome 11.4
6 athabaskan brainstem dysgenesis syndrome 11.3
7 encephalopathy, neonatal severe, due to mecp2 mutations 11.0
8 rohhad 10.9
9 medullary sponge kidney 10.8 GDNF RET
10 waardenburg syndrome type 4 10.7 EDN3 EDNRB
11 neonatal hypoxic and ischemic brain injury 10.6 BDNF TH
12 waardenburg syndrome, type 4a 10.6 EDN3 EDNRB RET
13 hypoganglionosis 10.6 GDNF RET TH
14 multiple endocrine neoplasia, type iib 10.6 EDNRB GDNF RET
15 peripheral nervous system neoplasm 10.5 BDNF PHOX2B TH
16 autonomic nervous system neoplasm 10.5 BDNF PHOX2B TH
17 cerebral artery occlusion 10.4 BDNF GDNF
18 thyroid carcinoma, familial medullary 10.4 EDNRB GDNF RET
19 synucleinopathy 10.4 BDNF GDNF TH
20 waardenburg's syndrome 10.4 EDN3 EDNRB RET
21 intestinal obstruction 10.4 EDN3 EDNRB GDNF RET
22 constipation 10.3 EDN3 EDNRB GDNF RET
23 intestinal pseudo-obstruction 10.3 EDNRB RET TLX2
24 central nervous system disease 10.3 BDNF GDNF TH
25 cochlear disease 10.3 EDN3 EDNRB
26 autonomic nervous system disease 10.3 ASCL1 EDNRB PHOX2A PHOX2B
27 pheochromocytoma 10.3 ASCL1 GDNF RET TH
28 thyroid cancer, nonmedullary, 2 10.3 EDNRB GDNF RET
29 nervous system disease 10.2 BDNF GDNF TH
30 goldberg-shprintzen syndrome 10.1 ASCL1 EDN3 EDNRB GDNF RET
31 anterior spinal artery syndrome 10.0
32 exotropia 10.0 PHOX2A PHOX2B
33 peyronie's disease 10.0
34 colonic disease 9.9 ASCL1 EDN3 EDNRB GDNF PHOX2B RET
35 nodular hidradenoma 9.9
36 hidradenoma 9.9
37 clear cell hidradenoma 9.9
38 sleep apnea 9.8
39 western equine encephalitis 9.8
40 central sleep apnea 9.8
41 encephalitis 9.8
42 hypersomnia 9.8
43 hypoglycemia 9.8
44 megacolon 9.7 EDN3 EDNRB GDNF PHOX2B RET TLX2

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



Diseases related to Central Hypoventilation Syndrome, Congenital

Symptoms & Phenotypes for Central Hypoventilation Syndrome, Congenital

Symptoms via clinical synopsis from OMIM:

57
Abdomen Gastrointestinal:
constipation
poor feeding
hirschsprung disease (16%)

Head And Neck Eyes:
diminished pupillary light responses

Skin Nails Hair Skin:
increased sweating

Metabolic Features:
poor temperature regulation
decreased basal body temperature

Neoplasia:
neuroblastoma
ganglioneuroma
ganglioneuroblastoma
tumors of the sympathetic nervous system (5 to 10%)

Respiratory:
alveolar hypoventilation
shallow breathing (decreased tidal volume)
normal respiratory rate
periods of apnea
abnormal respiration due to defect in autonomic function
more
Neurologic Central Nervous System:
dysfunction of the autonomic nervous system

Laboratory Abnormalities:
chronic hypoxemia
chronic hypercapnia


Clinical features from OMIM:

209880

Human phenotypes related to Central Hypoventilation Syndrome, Congenital:

59 32 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
2 seizures 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001250
3 muscular hypotonia 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001252
4 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
5 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
6 dysautonomia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002459
7 sensorineural hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000407
8 gastroesophageal reflux 59 32 frequent (33%) Frequent (79-30%) HP:0002020
9 cognitive impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0100543
10 strabismus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000486
11 aganglionic megacolon 59 32 occasional (7.5%) Occasional (29-5%),Very frequent (99-80%) HP:0002251
12 polyhydramnios 59 32 occasional (7.5%) Occasional (29-5%) HP:0001561
13 oligohydramnios 59 32 occasional (7.5%) Occasional (29-5%) HP:0001562
14 decreased fetal movement 59 32 occasional (7.5%) Occasional (29-5%) HP:0001558
15 neuroblastoma 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0003006
16 central hypoventilation 59 32 hallmark (90%) Very frequent (99-80%) HP:0007110
17 ganglioneuroma 59 32 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0003005
18 small for gestational age 59 32 hallmark (90%) Very frequent (99-80%) HP:0001518
19 ganglioneuroblastoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0006747
20 autonomic dysregulation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002271
21 central sleep apnea 59 32 hallmark (90%) Very frequent (99-80%) HP:0010536
22 breathing dysregulation 59 32 hallmark (90%) Very frequent (99-80%) HP:0005957
23 low-set ears 32 HP:0000369
24 hyperhidrosis 32 HP:0000975
25 constipation 32 HP:0002019
26 abnormality of the cardiovascular system 32 HP:0001626
27 feeding difficulties 32 HP:0011968
28 death in infancy 59 Frequent (79-30%)
29 abnormality of temperature regulation 32 HP:0004370
30 abnormality of the mouth 32 HP:0000153
31 downslanted palpebral fissures 32 HP:0000494
32 neoplasm of the central nervous system 59 Occasional (29-5%)
33 hypoventilation 32 HP:0002791
34 posteriorly rotated ears 32 HP:0000358
35 abnormality of the autonomic nervous system 59 Very frequent (99-80%)

UMLS symptoms related to Central Hypoventilation Syndrome, Congenital:


apnea, constipation, increased sweating, cheyne-stokes respiration, coughing, dyspnea, hemoptysis, hoarseness, signs and symptoms, respiratory, sneezing, shallow breathing, paradoxical respiration, hyperoxia

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 shRNA abundance <= 50% GR00343-S 9.32 GPR4 KCNK5 PHOX2A PHOX2B PMPCA RET

MGI Mouse Phenotypes related to Central Hypoventilation Syndrome, Congenital:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.25 ASCL1 BDNF DBX1 EDN3 EDNRB GDNF
2 growth/size/body region MP:0005378 10.17 ASCL1 BDNF DBX1 EDNRB GDNF KCNK5
3 mortality/aging MP:0010768 10.16 DBX1 EDN3 EDNRB GDNF GPR4 KCNK5
4 nervous system MP:0003631 10 ASCL1 BDNF DBX1 EDN3 EDNRB GDNF
5 digestive/alimentary MP:0005381 9.91 BDNF EDN3 EDNRB GDNF RET TLX2
6 no phenotypic analysis MP:0003012 9.56 ASCL1 BDNF DBX1 KCNK5 MARK3 PHOX2A
7 respiratory system MP:0005388 9.36 ASCL1 BDNF DBX1 EDNRB GPR4 KCNK5

Drugs & Therapeutics for Central Hypoventilation Syndrome, Congenital

Drugs for Central Hypoventilation Syndrome, Congenital (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Desogestrel Approved Phase 2, Phase 3,Not Applicable 54024-22-5 40973
2 Progestins Phase 2, Phase 3,Not Applicable
3 Contraceptive Agents Phase 2, Phase 3,Not Applicable
4 Contraceptives, Oral Phase 2, Phase 3,Not Applicable
5 Hormone Antagonists Phase 2, Phase 3,Not Applicable
6 Hormones Phase 2, Phase 3,Not Applicable
7 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3,Not Applicable
8 Estradiol valerate Approved, Investigational, Vet_approved Not Applicable 979-32-8
9
Estradiol Approved, Investigational, Vet_approved Not Applicable 50-28-2 5757
10
Ethinyl Estradiol Approved Not Applicable 57-63-6 5991
11
Polyestradiol phosphate Approved Not Applicable 28014-46-2
12 Contraceptives, Oral, Combined Not Applicable
13 Estradiol 17 beta-cypionate Not Applicable
14 Estradiol 3-benzoate Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Assessment of Desogestrel in Ondine Syndrome Completed NCT01243697 Phase 2, Phase 3 desogestrel
2 Therapeutic Effect of Desogestrel on Ventilatory Control in Patients With Congenital Central Hypoventilation Syndrome Unknown status NCT01500473 Not Applicable Desogestrel
3 PHOX2B Mutation-Confirmed Congenital Central Hypoventilation Syndrome in A Chinese Family: Presentations From Newborn to Adulthood Unknown status NCT00652964
4 Late-onset Congenital Central Hypoventilation Syndrome and the Mutation of Phox2B Gene Completed NCT01225679
5 International Congenital Central Hypoventilation Syndrome (CCHS) Registry Recruiting NCT03088020
6 Neurocognition in Congenital Central Hypoventilation Syndrome (CCHS) Recruiting NCT03568669
7 Evaluation of the Awakening Capability by a Vibrating Bracelet (BRASSARD) Recruiting NCT03053011 Not Applicable
8 Cognitive Consequences of an Activation of the Cortical Drive to Breath (VENTIPSY) Recruiting NCT03095729
9 European Home Mechanical Ventilation Registry Terminated NCT02315339

Search NIH Clinical Center for Central Hypoventilation Syndrome, Congenital

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Cochrane evidence based reviews: hypoventilation

Genetic Tests for Central Hypoventilation Syndrome, Congenital

Genetic tests related to Central Hypoventilation Syndrome, Congenital:

# Genetic test Affiliating Genes
1 Congenital Central Hypoventilation 29 ASCL1 BDNF EDN3 GDNF PHOX2B RET
2 Haddad Syndrome 29
3 Central Hypoventilation 29

Anatomical Context for Central Hypoventilation Syndrome, Congenital

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

41
Lung, Heart, Brain, Testes, Eye, Skin, Ciliary Ganglion

Publications for Central Hypoventilation Syndrome, Congenital

Articles related to Central Hypoventilation Syndrome, Congenital:

(show top 50) (show all 223)
# Title Authors Year
1
Congenital central hypoventilation syndrome: An overview of etiopathogenesis, associated pathologies, clinical presentation, and management. ( 29249648 )
2018
2
Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome. ( 28371199 )
2017
3
Three-Generation Family With Congenital Central Hypoventilation Syndrome and Novel <i>PHOX2B</i> Gene Non-Polyalanine Repeat Mutation. ( 28633714 )
2017
4
Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children. ( 26378991 )
2016
5
Significant phenotype variability of congenital central hypoventilation syndrome in a family with polyalanine expansion mutation of the PHOX2B gene. ( 27485184 )
2016
6
Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import. ( 27129232 )
2016
7
Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome. ( 27226447 )
2016
8
Genotype-phenotype relationship in Japanese patients with congenital central hypoventilation syndrome. ( 26063465 )
2015
9
Diaphragm Pacing without Tracheostomy in Congenital Central Hypoventilation Syndrome Patients. ( 25924848 )
2015
10
Thoracoscopic placement of phrenic nerve pacers for diaphragm pacing in congenital central hypoventilation syndrome. ( 25598098 )
2015
11
Dysregulation of locus coeruleus development in congenital central hypoventilation syndrome. ( 25975378 )
2015
12
Abnormal auditory pathways in PHOX2B mutation positive congenital central hypoventilation syndrome. ( 25886294 )
2015
13
Hyperthyroidism hidden by congenital central hypoventilation syndrome. ( 25581741 )
2015
14
Using non-invasive bi-level positive airway pressure ventilator via tracheostomy in children with congenital central hypoventilation syndrome: two case reports. ( 26109383 )
2015
15
Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome. ( 26011159 )
2015
16
[Congenital central hypoventilation syndrome: paradigm shifts and future prospects]. ( 24605541 )
2014
17
A case of congenital central hypoventilation syndrome with a novel mutation of the PHOX2B gene presenting as central sleep apnea. ( 24634632 )
2014
18
Ethical considerations with the management of congenital central hypoventilation syndrome. ( 25195933 )
2014
19
Late-onset congenital central hypoventilation syndrome and a rare PHOX2B gene mutation. ( 24792884 )
2014
20
Airway obstruction in congenital central hypoventilation syndrome. ( 24842348 )
2014
21
An assistive device for congenital central hypoventilation syndrome outpatients during sleep. ( 25069973 )
2014
22
A case of congenital central hypoventilation syndrome in a three-generation family with non-polyalanine repeat PHOX2B mutation. ( 24799442 )
2014
23
Congenital central hypoventilation syndrome and carbon dioxide sensitivity. ( 25319843 )
2014
24
The cerebral cost of breathing: an FMRI case-study in congenital central hypoventilation syndrome. ( 25268234 )
2014
25
Congenital central hypoventilation syndrome with PHOX2B mutation in Saudi Arabia: a- single center experience. ( 25505867 )
2014
26
Sleeping problems in mothers and fathers of patients suffering from congenital central hypoventilation syndrome. ( 25631640 )
2014
27
Congenital central hypoventilation syndrome: a neurocristopathy with disordered respiratory control and autonomic regulation. ( 25156769 )
2014
28
Extreme intra-familial variability of congenital central hypoventilation syndrome: a case series. ( 23622117 )
2013
29
Congenital central hypoventilation syndrome with PHOX2B gene mutation: are we missing the diagnosis? ( 22829249 )
2013
30
Congenital central hypoventilation syndrome and sudden infant death syndrome: disorders of autonomic regulation. ( 23465774 )
2013
31
An unusual cause of fetal hypomobility:congenital central hypoventilation syndrome associated with hirschsprung disease. ( 24135798 )
2013
32
Intermittent hyperglycemia due to autonomic nervous system dysfunction: a new feature in patients with congenital central hypoventilation syndrome. ( 22863257 )
2013
33
Neurally adjusted ventilatory assist (NAVA) mode as an adjunct diagnostic tool in congenital central hypoventilation syndrome. ( 23374524 )
2013
34
Thoracic paravertebral block for awake breast surgery in a patient with congenital central hypoventilation syndrome (Ondine's Curse). ( 23994702 )
2013
35
Congenital central hypoventilation syndrome; Safety of early transition to non-invasive ventilation. ( 23843332 )
2013
36
Transcriptional dysregulation and impairment of PHOX2B auto-regulatory mechanism induced by polyalanine expansion mutations associated with congenital central hypoventilation syndrome. ( 23103552 )
2013
37
Reversal of pulmonary hypertension after diaphragm pacing in an adult patient with congenital central hypoventilation syndrome. ( 23653299 )
2013
38
Peripheral chemoreceptors in congenital central hypoventilation syndrome. ( 23099221 )
2013
39
PHOX2B Mutation in a Taiwanese Newborn with Congenital Central Hypoventilation Syndrome. ( 23597545 )
2013
40
Congenital central hypoventilation syndrome. ( 23692929 )
2013
41
Diagnostic practices and disease surveillance in Canadian children with congenital central hypoventilation syndrome. ( 23762885 )
2013
42
Autonomic dysfunction of glucose homoeostasis in congenital central hypoventilation syndrome. ( 23231723 )
2013
43
A new device for the care of Congenital Central Hypoventilation Syndrome patients during sleep. ( 24110221 )
2013
44
Residual chemosensitivity to ventilatory challenges in genotyped congenital central hypoventilation syndrome. ( 24381123 )
2013
45
Monitoring diaphragm electrical activity and the detection of congenital central hypoventilation syndrome in a newborn. ( 24169930 )
2013
46
Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS). ( 22821709 )
2012
47
Vocal cord collapse during phrenic nerve-paced respiration in congenital central hypoventilation syndrome. ( 24358809 )
2012
48
Case reports of congenital central hypoventilation syndrome. ( 22564311 )
2012
49
Epidemiologic survey of patients with congenital central hypoventilation syndrome in Japan. ( 21958325 )
2012
50
Late-onset, insidious course and invasive treatment of congenital central hypoventilation syndrome in a case with the Phox2B mutation: case report. ( 22102181 )
2012

Variations for Central Hypoventilation Syndrome, Congenital

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

75
# Symbol AA change Variation ID SNP ID
1 BDNF p.Thr2Ile VAR_018260 rs8192466
2 PHOX2B p.Arg141Gln VAR_046900
3 PHOX2B p.Gln143Arg VAR_046901
4 RET p.Arg67His VAR_018153 rs192489011
5 RET p.Arg114His VAR_018154 rs76397662
6 RET p.Ala432Glu VAR_018155 rs552057730
7 RET p.Pro1039Leu VAR_018157 rs79853121

ClinVar genetic disease variations for Central Hypoventilation Syndrome, Congenital:

6
(show top 50) (show all 301)
# Gene Variation Type Significance SNP ID Assembly Location
1 PHOX2B NP_003915.2: p.Ala260(5_9) NT expansion Pathogenic
2 PHOX2B NM_003924.3(PHOX2B): c.618dupC (p.Ser207Glnfs) duplication Pathogenic rs587776626 GRCh37 Chromosome 4, 41748151: 41748151
3 PHOX2B NM_003924.3(PHOX2B): c.618dupC (p.Ser207Glnfs) duplication Pathogenic rs587776626 GRCh38 Chromosome 4, 41746134: 41746134
4 PHOX2B PHOX2B, 37-BP DEL, NT722 deletion Pathogenic
5 RET NM_020975.4(RET): c.2410G> A (p.Val804Met) single nucleotide variant Pathogenic rs79658334 GRCh37 Chromosome 10, 43614996: 43614996
6 RET NM_020975.4(RET): c.2410G> A (p.Val804Met) single nucleotide variant Pathogenic rs79658334 GRCh38 Chromosome 10, 43119548: 43119548
7 EDN3 EDN3, 1-BP INS, EX4 insertion Pathogenic
8 ASCL1 NM_004316.3(ASCL1): c.52C> A (p.Pro18Thr) single nucleotide variant Pathogenic rs267606667 GRCh37 Chromosome 12, 103352074: 103352074
9 ASCL1 NM_004316.3(ASCL1): c.52C> A (p.Pro18Thr) single nucleotide variant Pathogenic rs267606667 GRCh38 Chromosome 12, 102958296: 102958296
10 ASCL1 ASCL1, 15-BP DEL, NT111 deletion Pathogenic
11 ASCL1 ASCL1, 24-BP DEL, NT108 deletion Pathogenic
12 PHOX2B NM_003924.3(PHOX2B): c.762A> C (p.Ala254=) single nucleotide variant Benign rs17884724 GRCh37 Chromosome 4, 41748007: 41748007
13 PHOX2B NM_003924.3(PHOX2B): c.762A> C (p.Ala254=) single nucleotide variant Benign rs17884724 GRCh38 Chromosome 4, 41745990: 41745990
14 PHOX2B NM_003924.3(PHOX2B): c.870C> A (p.Pro290=) single nucleotide variant Benign rs17885864 GRCh37 Chromosome 4, 41747899: 41747899
15 PHOX2B NM_003924.3(PHOX2B): c.870C> A (p.Pro290=) single nucleotide variant Benign rs17885864 GRCh38 Chromosome 4, 41745882: 41745882
16 PHOX2B NM_003924.3(PHOX2B): c.741_755delCGCGGCAGCGGCGGC (p.Ala256_Ala260del) deletion Benign/Likely benign rs775006915 GRCh37 Chromosome 4, 41748014: 41748028
17 PHOX2B NM_003924.3(PHOX2B): c.741_755delCGCGGCAGCGGCGGC (p.Ala256_Ala260del) deletion Benign/Likely benign rs775006915 GRCh38 Chromosome 4, 41745997: 41746011
18 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh37 Chromosome 9, 139313082: 139313082
19 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh38 Chromosome 9, 136418630: 136418630
20 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh38 Chromosome 9, 136418847: 136418847
21 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh37 Chromosome 9, 139313299: 139313299
22 PHOX2B NM_003924.3(PHOX2B): c.741_758del18 (p.Ala255_Ala260del) deletion Benign/Likely benign rs771383153 GRCh37 Chromosome 4, 41748011: 41748028
23 PHOX2B NM_003924.3(PHOX2B): c.741_758del18 (p.Ala255_Ala260del) deletion Benign/Likely benign rs771383153 GRCh38 Chromosome 4, 41745994: 41746011
24 PHOX2B NM_003924.3(PHOX2B): c.726A> G (p.Ala242=) single nucleotide variant Benign/Likely benign rs757355779 GRCh37 Chromosome 4, 41748043: 41748043
25 PHOX2B NM_003924.3(PHOX2B): c.726A> G (p.Ala242=) single nucleotide variant Benign/Likely benign rs757355779 GRCh38 Chromosome 4, 41746026: 41746026
26 PHOX2B NM_003924.3(PHOX2B): c.552C> T (p.Ser184=) single nucleotide variant Benign/Likely benign rs17885216 GRCh38 Chromosome 4, 41746200: 41746200
27 PHOX2B NM_003924.3(PHOX2B): c.552C> T (p.Ser184=) single nucleotide variant Benign/Likely benign rs17885216 GRCh37 Chromosome 4, 41748217: 41748217
28 PHOX2B NM_003924.3(PHOX2B): c.450C> G (p.Arg150=) single nucleotide variant Benign rs17881486 GRCh38 Chromosome 4, 41746302: 41746302
29 PHOX2B NM_003924.3(PHOX2B): c.450C> G (p.Arg150=) single nucleotide variant Benign rs17881486 GRCh37 Chromosome 4, 41748319: 41748319
30 PHOX2B NM_003924.3(PHOX2B): c.832G> A (p.Gly278Ser) single nucleotide variant Likely benign rs138545772 GRCh37 Chromosome 4, 41747937: 41747937
31 PHOX2B NM_003924.3(PHOX2B): c.832G> A (p.Gly278Ser) single nucleotide variant Likely benign rs138545772 GRCh38 Chromosome 4, 41745920: 41745920
32 PHOX2B NM_003924.3(PHOX2B): c.765_779delGGCAGCGGCGGCAGC (p.Ala256_Ala260del) deletion Benign/Likely benign rs761018157 GRCh37 Chromosome 4, 41747990: 41748004
33 PHOX2B NM_003924.3(PHOX2B): c.765_779delGGCAGCGGCGGCAGC (p.Ala256_Ala260del) deletion Benign/Likely benign rs761018157 GRCh38 Chromosome 4, 41745973: 41745987
34 PHOX2B NM_003924.3(PHOX2B): c.756_776del21 (p.Ala254_Ala260del) deletion Benign/Likely benign rs17879189 GRCh37 Chromosome 4, 41747993: 41748013
35 PHOX2B NM_003924.3(PHOX2B): c.756_776del21 (p.Ala254_Ala260del) deletion Benign/Likely benign rs17879189 GRCh38 Chromosome 4, 41745976: 41745996
36 PHOX2B NM_003924.3(PHOX2B): c.738_776del39 (p.Ala248_Ala260del) deletion Benign/Likely benign rs757020181 GRCh37 Chromosome 4, 41747993: 41748031
37 PHOX2B NM_003924.3(PHOX2B): c.738_776del39 (p.Ala248_Ala260del) deletion Benign/Likely benign rs757020181 GRCh38 Chromosome 4, 41745976: 41746014
38 PHOX2B NM_003924.3(PHOX2B): c.741_761del21 (p.Ala254_Ala260del) deletion Benign rs780971967 GRCh37 Chromosome 4, 41748008: 41748028
39 PHOX2B NM_003924.3(PHOX2B): c.741_761del21 (p.Ala254_Ala260del) deletion Benign rs780971967 GRCh38 Chromosome 4, 41745991: 41746011
40 PHOX2B NM_003924.3(PHOX2B): c.760G> A (p.Ala254Thr) single nucleotide variant Uncertain significance rs766767855 GRCh37 Chromosome 4, 41748009: 41748009
41 PHOX2B NM_003924.3(PHOX2B): c.760G> A (p.Ala254Thr) single nucleotide variant Uncertain significance rs766767855 GRCh38 Chromosome 4, 41745992: 41745992
42 PHOX2B NM_003924.3(PHOX2B): c.750G> A (p.Ala250=) single nucleotide variant Benign/Likely benign rs17882335 GRCh37 Chromosome 4, 41748019: 41748019
43 PHOX2B NM_003924.3(PHOX2B): c.750G> A (p.Ala250=) single nucleotide variant Benign/Likely benign rs17882335 GRCh38 Chromosome 4, 41746002: 41746002
44 PHOX2B NM_003924.3(PHOX2B): c.681G> A (p.Ala227=) single nucleotide variant Likely benign rs878854617 GRCh37 Chromosome 4, 41748088: 41748088
45 PHOX2B NM_003924.3(PHOX2B): c.681G> A (p.Ala227=) single nucleotide variant Likely benign rs878854617 GRCh38 Chromosome 4, 41746071: 41746071
46 PHOX2B NM_003924.3(PHOX2B): c.639C> G (p.Gly213=) single nucleotide variant Likely benign rs17879258 GRCh38 Chromosome 4, 41746113: 41746113
47 PHOX2B NM_003924.3(PHOX2B): c.639C> G (p.Gly213=) single nucleotide variant Likely benign rs17879258 GRCh37 Chromosome 4, 41748130: 41748130
48 PHOX2B NM_003924.3(PHOX2B): c.234C> T (p.Tyr78=) single nucleotide variant Benign/Likely benign rs73810366 GRCh37 Chromosome 4, 41750394: 41750394
49 PHOX2B NM_003924.3(PHOX2B): c.234C> T (p.Tyr78=) single nucleotide variant Benign/Likely benign rs73810366 GRCh38 Chromosome 4, 41748377: 41748377
50 PHOX2B NM_003924.3(PHOX2B): c.135C> T (p.Asn45=) single nucleotide variant Likely benign rs878854616 GRCh38 Chromosome 4, 41748476: 41748476

Expression for Central Hypoventilation Syndrome, Congenital

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

Pathways for Central Hypoventilation Syndrome, Congenital

Pathways related to Central Hypoventilation Syndrome, Congenital according to KEGG:

37
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Neurotrophin signaling pathway hsa04722

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

# Super pathways Score Top Affiliating Genes
1 11.44 ASCL1 PHOX2B TLX2
2 11.38 ASCL1 BDNF PHOX2A PHOX2B RET TH
3 11.15 ASCL1 BDNF GDNF TH
4 10.81 ASCL1 RET TH

GO Terms for Central Hypoventilation Syndrome, Congenital

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

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.96 ASCL1 BDNF EDNRB GDNF RET
2 regulation of gene expression GO:0010468 9.84 ASCL1 EDN3 GDNF PHOX2B
3 neuron migration GO:0001764 9.75 ASCL1 PHOX2B TLX3
4 negative regulation of neuron differentiation GO:0045665 9.67 ASCL1 PHOX2B TLX3
5 neuron differentiation GO:0030182 9.65 ASCL1 EDN3 PHOX2B RET TLX3
6 dopaminergic neuron differentiation GO:0071542 9.61 PHOX2A PHOX2B
7 response to pain GO:0048265 9.61 EDNRB RET
8 melanocyte differentiation GO:0030318 9.6 EDN3 EDNRB
9 vasoconstriction GO:0042310 9.59 EDN3 EDNRB
10 glial cell differentiation GO:0010001 9.58 ASCL1 PHOX2B
11 peripheral nervous system development GO:0007422 9.58 BDNF EDNRB GDNF
12 neuron fate specification GO:0048665 9.57 ASCL1 TLX3
13 regulation of respiratory gaseous exchange by neurological system process GO:0002087 9.55 PHOX2B TLX3
14 sympathetic ganglion development GO:0061549 9.51 ASCL1 PHOX2B
15 noradrenergic neuron differentiation GO:0003357 9.48 PHOX2A PHOX2B
16 vein smooth muscle contraction GO:0014826 9.46 EDN3 EDNRB
17 neural crest cell migration GO:0001755 9.46 EDN3 EDNRB GDNF RET
18 noradrenergic neuron development GO:0003358 9.43 ASCL1 PHOX2B
19 posterior midgut development GO:0007497 9.37 EDNRB RET
20 parasympathetic nervous system development GO:0048486 9.32 PHOX2A PHOX2B
21 sympathetic nervous system development GO:0048485 9.26 ASCL1 GDNF PHOX2A PHOX2B
22 enteric nervous system development GO:0048484 9.02 EDNRB GDNF PHOX2B RET TLX2
23 multicellular organism development GO:0007275 10.07 ASCL1 DBX1 EDN3 PHOX2B RET TLX2

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

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.5 ASCL1 DBX1 PHOX2A PHOX2B TLX2 TLX3
2 sequence-specific DNA binding GO:0043565 9.1 ASCL1 DBX1 PHOX2A PHOX2B TLX2 TLX3

Sources for Central Hypoventilation Syndrome, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
37 KEGG
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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