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Congenital central hypoventilation

MedGen UID:
220902
Concept ID:
C1275808
Disease or Syndrome
Synonyms: Congenital Central Hypoventilation Syndrome; Congenital failure of autonomic control; Idiopathic congenital central alveolar hypoventilation; Primary alveolar hypoventilation
SNOMED CT: CCHS - Congenital central hypoventilation (399040002); Congenital pulmonary hypoventilation (399040002); Congenital central hypoventilation (399040002); Ondine curse (399040002)
 
Related genes: MYO1H, LBX1, PHOX2B
 
Monarch Initiative: MONDO:0800031
OMIM®: 209880
OMIM® Phenotypic series: PS209880

Disease characteristics

Excerpted from the GeneReview: Congenital Central Hypoventilation Syndrome
Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD) with the hallmark of disordered respiratory control. The age of initial recognition of CCHS ranges from neonatal onset (i.e., in the first 30 days of life) to (less commonly) later onset (from 1 month to adulthood). Neonatal-onset CCHS is characterized by apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; ANSD including decreased heart rate beat-to-beat variability and sinus pauses; altered temperature regulation; and altered pupillary response to light. Some children have altered development of neural crest-derived structures (i.e., Hirschsprung disease, altered esophageal motility/dysphagia, and severe constipation even in the absence of Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Neurocognitive delay is variable, and possibly influenced by cyanotic breath holding, prolonged sinus pauses, need for 24-hour/day artificial ventilation, and seizures. Later-onset CCHS is characterized by alveolar hypoventilation during sleep and attenuated manifestations of ANSD. [from GeneReviews]
Authors:
Debra E Weese-Mayer  |  Casey M Rand  |  Ilya Khaytin, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Congenital central hypoventilation syndrome (CCHS) is a disorder that affects normal 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 nervous system reaction is impaired in people with CCHS. 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.

Symptoms of CCHS usually become apparent shortly after birth when affected infants hypoventilate upon falling asleep. In these infants, a lack of oxygen in the blood often causes a bluish appearance of the skin or lips (cyanosis). In some milder cases, CCHS may not become apparent until later in life.

In addition to the breathing problem, people with CCHS may have difficulty regulating their heart rate and blood pressure, for example, in response to exercise or changes in body position. They also have decreased perception of pain, low body temperature, and occasional episodes of heavy sweating.

People with CCHS may have additional problems affecting the nervous system. About 20 percent of people with CCHS have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. (Some researchers refer to the combination of CCHS and Hirschsprung disease as Haddad syndrome.) Some affected individuals develop learning difficulties or other neurological problems. People with CCHS are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas.

Additionally, individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as "box-shaped."

In CCHS, life expectancy and the extent of any intellectual disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment.  https://medlineplus.gov/genetics/condition/congenital-central-hypoventilation-syndrome

Professional guidelines

PubMed

Trang H, Samuels M, Ceccherini I, Frerick M, Garcia-Teresa MA, Peters J, Schoeber J, Migdal M, Markstrom A, Ottonello G, Piumelli R, Estevao MH, Senecic-Cala I, Gnidovec-Strazisar B, Pfleger A, Porto-Abal R, Katz-Salamon M
Orphanet J Rare Dis 2020 Sep 21;15(1):252. doi: 10.1186/s13023-020-01460-2. PMID: 32958024Free PMC Article
Maloney MA, Kun SS, Keens TG, Perez IA
Expert Rev Respir Med 2018 Apr;12(4):283-292. Epub 2018 Feb 28 doi: 10.1080/17476348.2018.1445970. PMID: 29486608
Zaidi S, Gandhi J, Vatsia S, Smith NL, Khan SA
Auton Neurosci 2018 Mar;210:1-9. Epub 2017 Nov 13 doi: 10.1016/j.autneu.2017.11.003. PMID: 29249648

Recent clinical studies

Etiology

Finch CE, Leu RM, Harford KL, Westbrook AL, Kasi AS
J Clin Sleep Med 2023 Mar 1;19(3):549-554. doi: 10.5664/jcsm.10384. PMID: 36541215Free PMC Article
Dudoignon B, Denjoy I, Patout M, Matrot B, Gallego J, Bokov P, Delclaux C
Pediatr Res 2023 Mar;93(4):1003-1009. Epub 2022 Jul 26 doi: 10.1038/s41390-022-02215-4. PMID: 35882978
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Sleep 2022 Nov 9;45(11) doi: 10.1093/sleep/zsac166. PMID: 35878762
Tanizawa K, Chin K
Respir Investig 2018 Mar;56(2):111-119. Epub 2017 Dec 23 doi: 10.1016/j.resinv.2017.11.012. PMID: 29548648
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Semin Cell Dev Biol 2010 Oct;21(8):814-22. Epub 2010 Aug 4 doi: 10.1016/j.semcdb.2010.07.006. PMID: 20691277

Diagnosis

Montalva L, Cheng LS, Kapur R, Langer JC, Berrebi D, Kyrklund K, Pakarinen M, de Blaauw I, Bonnard A, Gosain A
Nat Rev Dis Primers 2023 Oct 12;9(1):54. doi: 10.1038/s41572-023-00465-y. PMID: 37828049
Dudoignon B, Denjoy I, Patout M, Matrot B, Gallego J, Bokov P, Delclaux C
Pediatr Res 2023 Mar;93(4):1003-1009. Epub 2022 Jul 26 doi: 10.1038/s41390-022-02215-4. PMID: 35882978
Trang H, Samuels M, Ceccherini I, Frerick M, Garcia-Teresa MA, Peters J, Schoeber J, Migdal M, Markstrom A, Ottonello G, Piumelli R, Estevao MH, Senecic-Cala I, Gnidovec-Strazisar B, Pfleger A, Porto-Abal R, Katz-Salamon M
Orphanet J Rare Dis 2020 Sep 21;15(1):252. doi: 10.1186/s13023-020-01460-2. PMID: 32958024Free PMC Article
Guyenet PG, Bayliss DA, Stornetta RL, Ludwig MG, Kumar NN, Shi Y, Burke PG, Kanbar R, Basting TM, Holloway BB, Wenker IC
J Physiol 2016 Mar 15;594(6):1529-51. Epub 2016 Feb 19 doi: 10.1113/JP271480. PMID: 26748771Free PMC Article
Guyenet PG, Stornetta RL, Bayliss DA
J Comp Neurol 2010 Oct 1;518(19):3883-906. doi: 10.1002/cne.22435. PMID: 20737591Free PMC Article

Therapy

Coghlan M, Richards E, Shaik S, Rossi P, Vanama RB, Ahmadi S, Petroz C, Crawford M, Maynes JT
Sci Rep 2018 Mar 27;8(1):5275. doi: 10.1038/s41598-018-23335-0. PMID: 29588456Free PMC Article
Basu SM, Chung FF, AbdelHakim SF, Wong J
Anesth Analg 2017 Jan;124(1):169-178. doi: 10.1213/ANE.0000000000001470. PMID: 27918326
Abdunnur SV, Kim DH
Prog Neurol Surg 2015;29:64-75. Epub 2015 Sep 4 doi: 10.1159/000434657. PMID: 26393957
Macey PM, Woo MA, Macey KE, Keens TG, Saeed MM, Alger JR, Harper RM
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Silvestri JM, Hanna BD, Volgman AS, Jones PJ, Barnes SD, Weese-Mayer DE
Pediatr Pulmonol 2000 May;29(5):351-8. doi: 10.1002/(sici)1099-0496(200005)29:5<351::aid-ppul3>3.0.co;2-z. PMID: 10790246

Prognosis

Diek D, Smidt MP, Mesman S
Int J Mol Sci 2022 Aug 17;23(16) doi: 10.3390/ijms23169260. PMID: 36012524Free PMC Article
Zhou A, Rand CM, Hockney SM, Niewijk G, Reineke P, Speare V, Berry-Kravis EM, Zhou L, Jennings LJ, Yu M, Ceccherini I, Bachetti T, Pennock M, Yap KL, Weese-Mayer DE
Genet Med 2021 Sep;23(9):1656-1663. Epub 2021 May 6 doi: 10.1038/s41436-021-01178-x. PMID: 33958749
Maloney MA, Kun SS, Keens TG, Perez IA
Expert Rev Respir Med 2018 Apr;12(4):283-292. Epub 2018 Feb 28 doi: 10.1080/17476348.2018.1445970. PMID: 29486608
Trang H, Dehan M, Beaufils F, Zaccaria I, Amiel J, Gaultier C; French CCHS Working Group
Chest 2005 Jan;127(1):72-9. doi: 10.1378/chest.127.1.72. PMID: 15653965
Weese-Mayer DE, Silvestri JM, Menzies LJ, Morrow-Kenny AS, Hunt CE, Hauptman SA
J Pediatr 1992 Mar;120(3):381-7. doi: 10.1016/s0022-3476(05)80901-1. PMID: 1538284

Clinical prediction guides

Lazarov NE, Atanasova DY
Adv Anat Embryol Cell Biol 2023;237:123-138. doi: 10.1007/978-3-031-44757-0_8. PMID: 37946080
Ghelab Z, Bokov P, Teissier N, Micaelli D, Patout M, Hayotte A, Dauger S, Delclaux C, Dudoignon B
Pediatr Pulmonol 2023 Jun;58(6):1761-1767. Epub 2023 Apr 4 doi: 10.1002/ppul.26399. PMID: 37014159
Finch CE, Leu RM, Harford KL, Westbrook AL, Kasi AS
J Clin Sleep Med 2023 Mar 1;19(3):549-554. doi: 10.5664/jcsm.10384. PMID: 36541215Free PMC Article
Diek D, Smidt MP, Mesman S
Int J Mol Sci 2022 Aug 17;23(16) doi: 10.3390/ijms23169260. PMID: 36012524Free PMC Article
Moore SW
Pediatr Surg Int 2012 Nov;28(11):1045-58. Epub 2012 Sep 23 doi: 10.1007/s00383-012-3175-6. PMID: 23001136

Recent systematic reviews

Slattery SM, Perez IA, Ceccherini I, Chen ML, Kurek KC, Yap KL, Keens TG, Khaytin I, Ballard HA, Sokol EA, Mittal A, Rand CM, Weese-Mayer DE
Clin Auton Res 2023 Jun;33(3):231-249. Epub 2022 Nov 20 doi: 10.1007/s10286-022-00908-8. PMID: 36403185
Basu SM, Chung FF, AbdelHakim SF, Wong J
Anesth Analg 2017 Jan;124(1):169-178. doi: 10.1213/ANE.0000000000001470. PMID: 27918326

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