CCHS
MCID: CNT097
MIFTS: 67

Central Hypoventilation Syndrome, Congenital (CCHS)

Categories: Blood diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Central Hypoventilation Syndrome, Congenital

MalaCards integrated aliases for Central Hypoventilation Syndrome, Congenital:

Name: Central Hypoventilation Syndrome, Congenital 58 76 56
Congenital Central Hypoventilation Syndrome 12 77 25 54 26 76 38 15
Cchs 58 12 77 54 26 60 76
Haddad Syndrome 58 26 60 30 6
Congenital Central Hypoventilation 26 30 6 74
Congenital Central Alveolar Hypoventilation Syndrome 12 60 74
Congenital Failure of Autonomic Control 54 26 76
Ondine Syndrome 12 26 60
Ondine Curse 12 60 76
Central Congenital Hypoventilation Syndrome 12 60
Central Hypoventilation Syndrome 58 13
Ondine-Hirschsprung Disease 26 60
Central Hypoventilation 30 6
Hypoventilation 45 74
Central Hypoventilation Syndrome, Congenital, with or Without Hirschsprung Disease 58
Congenital Central Alveolar Hypoventilation-Hirschsprung Disease Syndrome 60
Idiopathic Congenital Central Alveolar Hypoventilation 54
Syndrome, Hypoventilation, Central, Congenital 41
Primary Alveolar Hypoventilation Syndrome 38
Central Alveolar Hypoventilation Syndrome 74
Autonomic Control, Congenital Failure of 58
Sleep-Related Respiratory Failure 74
Primary Alveolar Hypoventilation 54
Cchs with Hirschsprung Disease 74
Ondine-Hirschsprung Syndrome 60
Ondine Curse, Congenital 58
Congenital Ondine Curse 54
Sleep Apnea, Central 74
Ondine's Curse 77

Characteristics:

Orphanet epidemiological data:

60
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:

58
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:

33
central hypoventilation syndrome, congenital:
Mortality/Aging death in infancy
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Penetrance for the phox2b polyalanine repeat expansion 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...

Classifications:



Summaries for Central Hypoventilation Syndrome, Congenital

NIH Rare Diseases : 54 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 constipation, dyspnea and apnea. 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 Contraceptive Agents have been mentioned in the context of this disorder. Affiliated tissues include lung, eye and heart, and related phenotypes are failure to thrive and respiratory insufficiency

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.

Genetics Home Reference : 26 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.

OMIM : 58 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 : 76 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.

Wikipedia : 77 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 top 50) (show all 208)
# Related Disease Score Top Affiliating Genes
1 hirschsprung disease 1 30.0 EDN3 EDNRB GDNF PHOX2B RET
2 sudden infant death syndrome 29.9 ASCL1 BDNF PHOX2A PHOX2B TH
3 obesity-hypoventilation syndrome 12.6
4 idiopathic alveolar hypoventilation syndrome 12.1
5 perry syndrome 11.6
6 athabaskan brainstem dysgenesis syndrome 11.4
7 nemaline myopathy 11.3
8 pulmonary hemosiderosis 11.2
9 rohhad 11.1
10 encephalopathy, neonatal severe, due to mecp2 mutations 11.1
11 nemaline myopathy 3 11.0
12 pontocerebellar hypoplasia, type 4 11.0
13 nemaline myopathy 2 11.0
14 nemaline myopathy 5 11.0
15 congenital disorder of glycosylation, type iib 11.0
16 nemaline myopathy 1 11.0
17 nemaline myopathy 4 11.0
18 pura syndrome 11.0
19 medullary sponge kidney 10.4 GDNF RET
20 waardenburg syndrome type 4 10.4 EDN3 EDNRB
21 oligomeganephronia 10.3 GDNF RET
22 neonatal hypoxic and ischemic brain injury 10.3 BDNF TH
23 reye syndrome 10.3
24 hypoganglionosis 10.3 GDNF RET TH
25 waardenburg syndrome, type 4a 10.3 EDN3 EDNRB RET
26 multiple endocrine neoplasia, type iib 10.3 EDNRB GDNF RET
27 waardenburg syndrome, type 4b 10.3 EDN3 EDNRB
28 nervous system disease 10.3 BDNF GDNF TH
29 cochlear disease 10.2 EDN3 EDNRB
30 autonomic nervous system neoplasm 10.2 BDNF PHOX2B TH
31 peripheral nervous system neoplasm 10.2 BDNF PHOX2B TH
32 anterior spinal artery syndrome 10.2
33 thyroid carcinoma, familial medullary 10.2 EDNRB GDNF RET
34 neuromuscular disease 10.2
35 waardenburg's syndrome 10.2 EDN3 EDNRB RET
36 cerebral artery occlusion 10.2 BDNF GDNF
37 sleep apnea 10.2
38 myotonic dystrophy 10.2
39 thyroid cancer, nonmedullary, 2 10.2 EDNRB GDNF RET
40 peyronie's disease 10.2
41 sexual disorder 10.2
42 intestinal obstruction 10.2 EDN3 EDNRB GDNF RET
43 constipation 10.2 EDN3 EDNRB GDNF RET
44 arteriovenous malformations of the brain 10.1
45 respiratory failure 10.1
46 arteriovenous malformation 10.1
47 glossopharyngeal neuralgia 10.1
48 optic nerve disease 10.1
49 ischemia 10.1
50 lateral medullary syndrome 10.1

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

Human phenotypes related to Central Hypoventilation Syndrome, Congenital:

60 33 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 60 33 hallmark (90%) Very frequent (99-80%) HP:0001508
2 respiratory insufficiency 60 33 hallmark (90%) Very frequent (99-80%) HP:0002093
3 strabismus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000486
4 aganglionic megacolon 60 33 occasional (7.5%) Occasional (29-5%),Very frequent (99-80%) HP:0002251
5 central hypoventilation 60 33 hallmark (90%) Very frequent (99-80%) HP:0007110
6 small for gestational age 60 33 hallmark (90%) Very frequent (99-80%) HP:0001518
7 central sleep apnea 60 33 hallmark (90%) Very frequent (99-80%) HP:0010536
8 breathing dysregulation 60 33 hallmark (90%) Very frequent (99-80%) HP:0005957
9 abnormal autonomic nervous system physiology 33 hallmark (90%) HP:0012332
10 intellectual disability 60 33 frequent (33%) Frequent (79-30%) HP:0001249
11 seizures 60 33 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001250
12 muscular hypotonia 60 33 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001252
13 gastroesophageal reflux 60 33 frequent (33%) Frequent (79-30%) HP:0002020
14 sensorineural hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0000407
15 cognitive impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0100543
16 polyhydramnios 60 33 occasional (7.5%) Occasional (29-5%) HP:0001561
17 oligohydramnios 60 33 occasional (7.5%) Occasional (29-5%) HP:0001562
18 decreased fetal movement 60 33 occasional (7.5%) Occasional (29-5%) HP:0001558
19 neuroblastoma 60 33 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0003006
20 ganglioneuroma 60 33 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0003005
21 ganglioneuroblastoma 60 33 occasional (7.5%) Occasional (29-5%) HP:0006747
22 low-set ears 33 HP:0000369
23 hyperhidrosis 33 HP:0000975
24 constipation 33 HP:0002019
25 dysautonomia 60 Very frequent (99-80%)
26 abnormality of the cardiovascular system 33 HP:0001626
27 feeding difficulties 33 HP:0011968
28 death in infancy 60 Frequent (79-30%)
29 abnormality of temperature regulation 33 HP:0004370
30 apnea 33 HP:0002104
31 abnormality of the mouth 33 HP:0000153
32 downslanted palpebral fissures 33 HP:0000494
33 neoplasm of the central nervous system 60 Occasional (29-5%)
34 hypoxemia 33 HP:0012418
35 hypoventilation 33 HP:0002791
36 hypercapnia 33 HP:0012416
37 posteriorly rotated ears 33 HP:0000358
38 abnormality of the autonomic nervous system 60 Very frequent (99-80%)
39 autonomic dysregulation 60 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM:

58
Abdomen Gastrointestinal:
constipation
poor feeding
hirschsprung disease (16%)

Skin Nails Hair Skin:
increased sweating

Respiratory:
alveolar hypoventilation
shallow breathing (decreased tidal volume)
normal respiratory rate
periods of apnea
abnormal respiration due to defect in autonomic function
more
Metabolic Features:
poor temperature regulation
decreased basal body temperature

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

Head And Neck Eyes:
diminished pupillary light responses

Neurologic Central Nervous System:
dysfunction of the autonomic nervous system

Laboratory Abnormalities:
chronic hypoxemia
chronic hypercapnia

Clinical features from OMIM:

209880

UMLS symptoms related to Central Hypoventilation Syndrome, Congenital:


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

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

27
# 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:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.3 ASCL1 BDNF DBH DBX1 EDN3 EDNRB
2 growth/size/body region MP:0005378 10.28 ASCL1 BDNF DBH DBX1 EDNRB GDNF
3 mortality/aging MP:0010768 10.19 ASCL1 BDNF DBH DBX1 EDN3 EDNRB
4 homeostasis/metabolism MP:0005376 10.15 BDNF DBH DBX1 EDNRB GPR4 KCNK5
5 nervous system MP:0003631 10.03 ASCL1 BDNF DBH DBX1 EDN3 EDNRB
6 digestive/alimentary MP:0005381 9.98 BDNF EDN3 EDNRB GDNF RET TLX2
7 integument MP:0010771 9.92 ASCL1 BDNF DBH EDN3 EDNRB GPR4
8 no phenotypic analysis MP:0003012 9.56 ASCL1 BDNF DBX1 KCNK5 MARK3 PHOX2A
9 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 Contraceptive Agents Phase 2, Phase 3,Not Applicable
3 Hormones 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 Progestins Phase 2, Phase 3,Not Applicable
7 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2, Phase 3,Not Applicable
8
Polyestradiol phosphate Approved Not Applicable 28014-46-2
9
Estradiol Approved, Investigational, Vet_approved Not Applicable 50-28-2 5757
10
Ethinyl Estradiol Approved Not Applicable 57-63-6 5991
11
Metronidazole Approved 443-48-1 4173
12 Contraceptives, Oral, Combined Not Applicable
13 Estradiol 3-benzoate Not Applicable
14 Estradiol 17 beta-cypionate 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 74 / NDF-RT 52 :


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 30 ASCL1 EDN3 GDNF PHOX2B RET
2 Haddad Syndrome 30
3 Central Hypoventilation 30

Anatomical Context for Central Hypoventilation Syndrome, Congenital

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

42
Lung, Eye, Heart, Brain, Testes, Skin, Cerebellum

Publications for Central Hypoventilation Syndrome, Congenital

Articles related to Central Hypoventilation Syndrome, Congenital:

(show top 50) (show all 257)
# Title Authors Year
1
Congenital central hypoventilation syndrome and Hirschsprung disease: A retrospective review of the French National Registry Center on 33 cases. ( 30879749 )
2019
2
Congenital central hypoventilation syndrome: Severe disease caused by co-occurrence of two PHOX2B variants inherited separately from asymptomatic family members. ( 30672101 )
2019
3
Novel PHOX2B mutations in congenital central hypoventilation syndrome. ( 30786110 )
2019
4
A Novel c.676_677insG PHOX2B Mutation in Congenital Central Hypoventilation Syndrome. ( 30853048 )
2019
5
Congenital central hypoventilation syndrome: An overview of etiopathogenesis, associated pathologies, clinical presentation, and management. ( 29249648 )
2018
6
Obstructive Sleep Apnea in Patients With Congenital Central Hypoventilation Syndrome Ventilated by Diaphragm Pacing Without Tracheostomy. ( 29351818 )
2018
7
Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome. ( 29098737 )
2018
8
Congenital central hypoventilation syndrome: Broader cognitive deficits revealed by parent controls. ( 29327497 )
2018
9
Congenital central hypoventilation syndrome: diagnosis and management. ( 29486608 )
2018
10
Congenital central hypoventilation syndrome mimicking mitochondrial disease. ( 29531718 )
2018
11
Medico-legal investigation in an explicable case of congenital central hypoventilation syndrome due to a rare variant of the PHOX2B gene. ( 29679838 )
2018
12
Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions. ( 29696799 )
2018
13
Systemic oxidative stress in congenital central hypoventilation syndrome. ( 30209197 )
2018
14
A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. ( 30227298 )
2018
15
Perioperative anesthetic management of children with congenital central hypoventilation syndrome and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation undergoing thoracoscopic phrenic nerve-diaphragm pacemaker implantation. ( 30251310 )
2018
16
Dysregulated glucose homeostasis in congenital central hypoventilation syndrome. ( 30447143 )
2018
17
Clinical approach to cardiac pauses in congenital central hypoventilation syndrome. ( 30461223 )
2018
18
Adult With PHOX2B Mutation and Late-Onset Congenital Central Hypoventilation Syndrome. ( 30518452 )
2018
19
The genetics of congenital central hypoventilation syndrome: clinical implications. ( 30532577 )
2018
20
Neuropsychological profile and social cognition in congenital central hypoventilation syndrome (CCHS): Correlation with neuroimaging in a clinical case. ( 28708033 )
2018
21
Congenital central hypoventilation syndrome: A pictorial demonstration of absent electrical diaphragmatic activity using non-invasive neurally adjusted ventilatory assist. ( 28851075 )
2018
22
Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome. ( 28371199 )
2017
23
Three-Generation Family With Congenital Central Hypoventilation Syndrome and Novel <i>PHOX2B</i> Gene Non-Polyalanine Repeat Mutation. ( 28633714 )
2017
24
Conscious sedation with dexmedetomidine for implantation of a phrenic nerve stimulator in a pediatric case of late-onset congenital central hypoventilation syndrome. ( 29457090 )
2017
25
Congenital central hypoventilation syndrome: a bedside-to-bench success story for advancing early diagnosis and treatment and improved survival and quality of life. ( 27673423 )
2017
26
Challenges in congenital central hypoventilation syndrome (Ondine's curse) on pregnancy: a case report. ( 27866447 )
2017
27
Anesthetic Considerations for Patients With Congenital Central Hypoventilation Syndrome: A Systematic Review of the Literature. ( 27918326 )
2017
28
Intelligent volume-assured pressured support (iVAPS) for the treatment of congenital central hypoventilation syndrome. ( 28190166 )
2017
29
Carbamazepine Improves Apneic Episodes in Congenital Central Hypoventilation Syndrome (CCHS) With a Novel PHOX2B Exon 1 Missense Mutation. ( 28992836 )
2017
30
Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children. ( 26378991 )
2016
31
Significant phenotype variability of congenital central hypoventilation syndrome in a family with polyalanine expansion mutation of the PHOX2B gene. ( 27485184 )
2016
32
Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import. ( 27129232 )
2016
33
Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome. ( 27226447 )
2016
34
Congenital Tonic Pupils Associated With Congenital Central Hypoventilation Syndrome and Hirschsprung Disease. ( 27340804 )
2016
35
Congenital central hypoventilation syndrome (CCHS): Circadian temperature variation. ( 26086998 )
2016
36
Dental treatment of a child with congenital central hypoventilation syndrome. ( 26702938 )
2016
37
Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review. ( 26838603 )
2016
38
An Infant with Congenital Central Hypoventilation Syndrome: Transient Burst Suppression Electroencephalogram. ( 26916541 )
2016
39
Pitfalls of open-access sleep medicine: a case of missed congenital central hypoventilation syndrome. ( 27031401 )
2016
40
Congenital central hypoventilation syndrome: diagnostic and management challenges. ( 29388615 )
2016
41
Genotype-phenotype relationship in Japanese patients with congenital central hypoventilation syndrome. ( 26063465 )
2015
42
Diaphragm Pacing without Tracheostomy in Congenital Central Hypoventilation Syndrome Patients. ( 25924848 )
2015
43
Thoracoscopic placement of phrenic nerve pacers for diaphragm pacing in congenital central hypoventilation syndrome. ( 25598098 )
2015
44
Dysregulation of locus coeruleus development in congenital central hypoventilation syndrome. ( 25975378 )
2015
45
Abnormal auditory pathways in PHOX2B mutation positive congenital central hypoventilation syndrome. ( 25886294 )
2015
46
Hyperthyroidism hidden by congenital central hypoventilation syndrome. ( 25581741 )
2015
47
Using non-invasive bi-level positive airway pressure ventilator via tracheostomy in children with congenital central hypoventilation syndrome: two case reports. ( 26109383 )
2015
48
Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome. ( 26011159 )
2015
49
Novel mutation-deletion in the PHOX2B gene of the patient diagnosed with Neuroblastoma, Hirschsprung's Disease, and Congenital Central Hypoventilation Syndrome (NB-HSCR-CCHS) Cluster. ( 26798564 )
2015
50
Health-related quality of life in young adults with congenital central hypoventilation syndrome due to PHOX2B mutations: a cross-sectional study. ( 26122307 )
2015

Variations for Central Hypoventilation Syndrome, Congenital

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

76
# 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 358)
# Gene Variation Type Significance SNP ID Assembly Location
1 PHOX2B NM_003924.3(PHOX2B): c.762A> C (p.Ala254=) single nucleotide variant Benign rs17884724 GRCh37 Chromosome 4, 41748007: 41748007
2 PHOX2B NM_003924.3(PHOX2B): c.762A> C (p.Ala254=) single nucleotide variant Benign rs17884724 GRCh38 Chromosome 4, 41745990: 41745990
3 PHOX2B NM_003924.3(PHOX2B): c.870C> A (p.Pro290=) single nucleotide variant Benign rs17885864 GRCh37 Chromosome 4, 41747899: 41747899
4 PHOX2B NM_003924.3(PHOX2B): c.870C> A (p.Pro290=) single nucleotide variant Benign rs17885864 GRCh38 Chromosome 4, 41745882: 41745882
5 PHOX2B NM_003924.3(PHOX2B): c.741_755delCGCGGCAGCGGCGGC (p.Ala256_Ala260del) deletion Benign/Likely benign rs775006915 GRCh37 Chromosome 4, 41748014: 41748028
6 PHOX2B NM_003924.3(PHOX2B): c.741_755delCGCGGCAGCGGCGGC (p.Ala256_Ala260del) deletion Benign/Likely benign rs775006915 GRCh38 Chromosome 4, 41745997: 41746011
7 PHOX2B NP_003915.2: p.Ala260(5_9) NT expansion Pathogenic
8 PHOX2B NM_003924.3(PHOX2B): c.618dupC (p.Ser207Glnfs) duplication Pathogenic rs587776626 GRCh37 Chromosome 4, 41748151: 41748151
9 PHOX2B NM_003924.3(PHOX2B): c.618dupC (p.Ser207Glnfs) duplication Pathogenic rs587776626 GRCh38 Chromosome 4, 41746134: 41746134
10 PHOX2B PHOX2B, 37-BP DEL, NT722 deletion Pathogenic
11 PHOX2B NM_003924.3(PHOX2B): c.299G> T (p.Arg100Leu) single nucleotide variant Uncertain significance rs104893855 GRCh37 Chromosome 4, 41749496: 41749496
12 PHOX2B NM_003924.3(PHOX2B): c.299G> T (p.Arg100Leu) single nucleotide variant Uncertain significance rs104893855 GRCh38 Chromosome 4, 41747479: 41747479
13 GDNF NM_000514.3(GDNF): c.277C> T (p.Arg93Trp) single nucleotide variant Likely benign rs36119840 GRCh37 Chromosome 5, 37816112: 37816112
14 GDNF NM_000514.3(GDNF): c.277C> T (p.Arg93Trp) single nucleotide variant Likely benign rs36119840 GRCh38 Chromosome 5, 37816010: 37816010
15 RET NM_020975.4(RET): c.2410G> A (p.Val804Met) single nucleotide variant Pathogenic/Likely pathogenic rs79658334 GRCh37 Chromosome 10, 43614996: 43614996
16 RET NM_020975.4(RET): c.2410G> A (p.Val804Met) single nucleotide variant Pathogenic/Likely pathogenic rs79658334 GRCh38 Chromosome 10, 43119548: 43119548
17 RET NM_020975.4(RET): c.341G> A (p.Arg114His) single nucleotide variant Benign rs76397662 GRCh37 Chromosome 10, 43597793: 43597793
18 RET NM_020975.4(RET): c.341G> A (p.Arg114His) single nucleotide variant Benign rs76397662 GRCh38 Chromosome 10, 43102345: 43102345
19 BDNF NM_170731.4(BDNF): c.29C> T (p.Thr10Ile) single nucleotide variant Uncertain significance rs8192466 GRCh37 Chromosome 11, 27680107: 27680107
20 BDNF NM_170731.4(BDNF): c.29C> T (p.Thr10Ile) single nucleotide variant Uncertain significance rs8192466 GRCh38 Chromosome 11, 27658560: 27658560
21 ASCL1 NM_004316.3(ASCL1): c.52C> A (p.Pro18Thr) single nucleotide variant Pathogenic rs267606667 GRCh37 Chromosome 12, 103352074: 103352074
22 ASCL1 NM_004316.3(ASCL1): c.52C> A (p.Pro18Thr) single nucleotide variant Pathogenic rs267606667 GRCh38 Chromosome 12, 102958296: 102958296
23 ASCL1 ASCL1, 15-BP DEL, NT111 deletion Pathogenic
24 ASCL1 ASCL1, 24-BP DEL, NT108 deletion Pathogenic
25 RET NM_020630.5(RET): c.2611G> A (p.Val871Ile) single nucleotide variant Uncertain significance rs145170911 GRCh37 Chromosome 10, 43615532: 43615532
26 RET NM_020630.5(RET): c.2611G> A (p.Val871Ile) single nucleotide variant Uncertain significance rs145170911 GRCh38 Chromosome 10, 43120084: 43120084
27 PHOX2B NM_003924.3(PHOX2B): c.826G> A (p.Gly276Ser) single nucleotide variant Uncertain significance rs587778607 GRCh38 Chromosome 4, 41745926: 41745926
28 PHOX2B NM_003924.3(PHOX2B): c.826G> A (p.Gly276Ser) single nucleotide variant Uncertain significance rs587778607 GRCh37 Chromosome 4, 41747943: 41747943
29 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh37 Chromosome 9, 139313082: 139313082
30 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh38 Chromosome 9, 136418630: 136418630
31 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh38 Chromosome 9, 136418847: 136418847
32 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh37 Chromosome 9, 139313299: 139313299
33 EDN3 NM_207034.2(EDN3): c.565dup (p.Thr189Asnfs) duplication Conflicting interpretations of pathogenicity rs11570344 GRCh38 Chromosome 20, 59322394: 59322394
34 EDN3 NM_207034.2(EDN3): c.565dup (p.Thr189Asnfs) duplication Conflicting interpretations of pathogenicity rs11570344 GRCh37 Chromosome 20, 57897449: 57897449
35 PHOX2B NM_003924.3(PHOX2B): c.591C> G (p.Gly197=) single nucleotide variant Likely benign rs144414806 GRCh37 Chromosome 4, 41748178: 41748178
36 PHOX2B NM_003924.3(PHOX2B): c.591C> G (p.Gly197=) single nucleotide variant Likely benign rs144414806 GRCh38 Chromosome 4, 41746161: 41746161
37 PHOX2B NM_003924.3(PHOX2B): c.288C> G (p.Arg96=) single nucleotide variant Benign/Likely benign rs201892150 GRCh37 Chromosome 4, 41749507: 41749507
38 PHOX2B NM_003924.3(PHOX2B): c.288C> G (p.Arg96=) single nucleotide variant Benign/Likely benign rs201892150 GRCh38 Chromosome 4, 41747490: 41747490
39 PHOX2B NM_003924.3(PHOX2B): c.*1486T> C single nucleotide variant Likely benign rs530550940 GRCh38 Chromosome 4, 41744321: 41744321
40 PHOX2B NM_003924.3(PHOX2B): c.*1486T> C single nucleotide variant Likely benign rs530550940 GRCh37 Chromosome 4, 41746338: 41746338
41 PHOX2B NM_003924.3(PHOX2B): c.*1387C> T single nucleotide variant Benign rs11723860 GRCh38 Chromosome 4, 41744420: 41744420
42 PHOX2B NM_003924.3(PHOX2B): c.*1387C> T single nucleotide variant Benign rs11723860 GRCh37 Chromosome 4, 41746437: 41746437
43 PHOX2B NM_003924.3(PHOX2B): c.*1269A> G single nucleotide variant Uncertain significance rs886059412 GRCh38 Chromosome 4, 41744538: 41744538
44 PHOX2B NM_003924.3(PHOX2B): c.*1269A> G single nucleotide variant Uncertain significance rs886059412 GRCh37 Chromosome 4, 41746555: 41746555
45 PHOX2B NM_003924.3(PHOX2B): c.*674dupT duplication Benign rs397840867 GRCh38 Chromosome 4, 41745133: 41745133
46 PHOX2B NM_003924.3(PHOX2B): c.*674dupT duplication Benign rs397840867 GRCh37 Chromosome 4, 41747150: 41747150
47 PHOX2B NM_003924.3(PHOX2B): c.*18G> A single nucleotide variant Uncertain significance rs776498322 GRCh38 Chromosome 4, 41745789: 41745789
48 PHOX2B NM_003924.3(PHOX2B): c.*18G> A single nucleotide variant Uncertain significance rs776498322 GRCh37 Chromosome 4, 41747806: 41747806
49 PHOX2B NM_003924.3(PHOX2B): c.-195G> A single nucleotide variant Uncertain significance rs775569375 GRCh38 Chromosome 4, 41748805: 41748805
50 PHOX2B NM_003924.3(PHOX2B): c.-195G> A single nucleotide variant Uncertain significance rs775569375 GRCh37 Chromosome 4, 41750822: 41750822

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:

38
# 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
5
Show member pathways
10.66 DBH TH

GO Terms for Central Hypoventilation Syndrome, Congenital

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

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.97 ASCL1 BDNF EDNRB GDNF RET
2 regulation of gene expression GO:0010468 9.86 ASCL1 EDN3 GDNF PHOX2B
3 neuron migration GO:0001764 9.79 ASCL1 PHOX2B TLX3
4 memory GO:0007613 9.74 BDNF DBH TH
5 negative regulation of neuron differentiation GO:0045665 9.71 ASCL1 PHOX2B TLX3
6 neuron differentiation GO:0030182 9.65 ASCL1 EDN3 PHOX2B RET TLX3
7 dopaminergic neuron differentiation GO:0071542 9.62 PHOX2A PHOX2B
8 melanocyte differentiation GO:0030318 9.62 EDN3 EDNRB
9 glial cell differentiation GO:0010001 9.61 ASCL1 PHOX2B
10 peripheral nervous system development GO:0007422 9.61 BDNF EDNRB GDNF
11 vasoconstriction GO:0042310 9.6 EDN3 EDNRB
12 neuron fate specification GO:0048665 9.59 ASCL1 TLX3
13 regulation of respiratory gaseous exchange by neurological system process GO:0002087 9.58 PHOX2B TLX3
14 sympathetic ganglion development GO:0061549 9.55 ASCL1 PHOX2B
15 catecholamine biosynthetic process GO:0042423 9.52 DBH TH
16 norepinephrine biosynthetic process GO:0042421 9.51 DBH TH
17 response to pain GO:0048265 9.5 DBH EDNRB RET
18 noradrenergic neuron differentiation GO:0003357 9.49 PHOX2A PHOX2B
19 vein smooth muscle contraction GO:0014826 9.48 EDN3 EDNRB
20 noradrenergic neuron development GO:0003358 9.46 ASCL1 PHOX2B
21 neural crest cell migration GO:0001755 9.46 EDN3 EDNRB GDNF RET
22 parasympathetic nervous system development GO:0048486 9.4 PHOX2A PHOX2B
23 posterior midgut development GO:0007497 9.37 EDNRB RET
24 sympathetic nervous system development GO:0048485 9.26 ASCL1 GDNF PHOX2A PHOX2B
25 enteric nervous system development GO:0048484 9.02 EDNRB GDNF PHOX2B RET TLX2
26 multicellular organism development GO:0007275 10.1 ASCL1 DBX1 EDN3 PHOX2B TLX2 TLX3

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

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific 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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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