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Central hypoventilation syndrome, congenital, 3(CCHS3)

MedGen UID:
1794174
•Concept ID:
C5561964
•
Disease or Syndrome
Synonym: CCHS3
 
Gene (location): LBX1 (10q24.32)
 
Monarch Initiative: MONDO:0030539
OMIM®: 619483

Definition

Congenital central hypoventilation syndrome-3 (CCHS3) is an autosomal recessive disorder characterized by slow and shallow breathing due to a deficiency in autonomic control of respiration. Affected individuals present in the neonatal period with respiratory insufficiency and absence of the hypercapnic reflex that stimulates breathing. Patients also have gastrointestinal problems manifest as feeding difficulties and diarrhea or constipation. Other features may include poor heat tolerance and paroxysmal hypertension (Hernandez-Miranda et al., 2018). For a discussion of genetic heterogeneity of CCHS, see CCHS1 (209880). [from OMIM]

Clinical features

From HPO
Episodic hypertension
MedGen UID:
347389
•Concept ID:
C1857175
•
Finding
See: Feature record | Search on this feature
Feeding difficulties
MedGen UID:
65429
•Concept ID:
C0232466
•
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
See: Feature record | Search on this feature
Chronic constipation
MedGen UID:
98325
•Concept ID:
C0401149
•
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
See: Feature record | Search on this feature
Episodic vomiting
MedGen UID:
333228
•Concept ID:
C1838993
•
Finding
Paroxysmal, recurrent episodes of vomiting.
See: Feature record | Search on this feature
Apnea
MedGen UID:
2009
•Concept ID:
C0003578
•
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
See: Feature record | Search on this feature
Respiratory failure
MedGen UID:
257837
•Concept ID:
C1145670
•
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
See: Feature record | Search on this feature
Central hypoventilation
MedGen UID:
812169
•Concept ID:
C3805839
•
Finding
See: Feature record | Search on this feature
Heat intolerance
MedGen UID:
66659
•Concept ID:
C0231274
•
Pathologic Function
The inability to maintain a comfortable body temperature in warm or hot weather.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Annual Respiratory Evaluations in Congenital Central Hypoventilation Syndrome and Changes in Ventilatory Management.
Shah AS, Leu RM, Keens TG, Kasi AS
Pediatr Allergy Immunol Pulmonol 2021 Sep;34(3):97-101. Epub 2021 Aug 27 doi: 10.1089/ped.2021.0072. PMID: 34449269Free PMC Article
Neurocognition in Congenital Central Hypoventilation Syndrome: influence of genotype and ventilation method.
Trang H, Bourgeois P, Cheliout-Heraut F
Orphanet J Rare Dis 2020 Nov 17;15(1):322. doi: 10.1186/s13023-020-01601-7. PMID: 33203435Free PMC Article
Management of Rare Causes of Pediatric Chronic Respiratory Failure.
Shi J, Al-Shamli N, Chiang J, Amin R
Sleep Med Clin 2020 Dec;15(4):511-526. Epub 2020 Sep 30 doi: 10.1016/j.jsmc.2020.07.002. PMID: 33131661

Recent clinical studies

Etiology

Neuroblastoma Predisposition and Surveillance-An Update from the 2023 AACR Childhood Cancer Predisposition Workshop.
Kamihara J, Diller LR, Foulkes WD, Michaeli O, Nakano Y, Pajtler KW, Perrino M, Scollon SR, Stewart DR, Voss S, Weksberg R, Hansford JR, Brodeur GM
Clin Cancer Res 2024 Aug 1;30(15):3137-3143. doi: 10.1158/1078-0432.CCR-24-0237. PMID: 38860978
Decannulation in congenital central hypoventilation syndrome.
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
Gender differences in obesity hypoventilation syndrome.
Barbagelata E, Ambrosino I, Díaz DE Terán T, González M, Nicolini A, Banfi P, Ferraioli G, Solidoro P
Minerva Med 2023 Jun;114(3):372-378. Epub 2022 Oct 31 doi: 10.23736/S0026-4806.22.08261-1. PMID: 36315241
Congenital central hypoventilation syndrome and ventilatory responses during cardiopulmonary exercise testing.
Sunkonkit K, Chiang J, Moraes TJ, To W, Schneiderman JE, Cifra B, Amin R
Pediatr Pulmonol 2021 Jun;56(6):1694-1703. Epub 2021 Feb 1 doi: 10.1002/ppul.25278. PMID: 33524248
Genetic diseases: congenital central hypoventilation, Rett, and Prader-Willi syndromes.
Gallego J
Compr Physiol 2012 Jul;2(3):2255-79. doi: 10.1002/cphy.c100037. PMID: 23723037

Diagnosis

Congenital Central Hypoventilation Syndrome and Disorders of Control of Ventilation.
Kasi AS, Perez IA
Clin Chest Med 2024 Sep;45(3):663-673. doi: 10.1016/j.ccm.2024.02.018. PMID: 39069329
The future of rare autonomic disease research.
Rand CM, Weese-Mayer DE
Clin Auton Res 2023 Jun;33(3):211-213. doi: 10.1007/s10286-023-00957-7. PMID: 37273037Free PMC Article
Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): a collaborative review of the current understanding.
Khaytin I, Victor AK, Barclay SF, Benson LA, Slattery SM, Rand CM, Kurek KC, Weese-Mayer DE
Clin Auton Res 2023 Jun;33(3):251-268. Epub 2023 May 10 doi: 10.1007/s10286-023-00936-y. PMID: 37162653
Gender differences in obesity hypoventilation syndrome.
Barbagelata E, Ambrosino I, Díaz DE Terán T, González M, Nicolini A, Banfi P, Ferraioli G, Solidoro P
Minerva Med 2023 Jun;114(3):372-378. Epub 2022 Oct 31 doi: 10.23736/S0026-4806.22.08261-1. PMID: 36315241
Pregnancy in congenital central hypoventilation syndrome.
Maloney MA, Keens TG, Vanderlaan MB, Perez IA
Am J Obstet Gynecol MFM 2020 Nov;2(4):100237. Epub 2020 Sep 21 doi: 10.1016/j.ajogmf.2020.100237. PMID: 33345936

Therapy

Normal sleep on mechanical ventilation in adult patients with congenital central alveolar hypoventilation (Ondine's curse syndrome).
Attali V, Straus C, Pottier M, Buzare MA, Morélot-Panzini C, Arnulf I, Similowski T
Orphanet J Rare Dis 2017 Jan 23;12(1):18. doi: 10.1186/s13023-017-0569-5. PMID: 28115003Free PMC Article
Anesthetic Considerations for Patients With Congenital Central Hypoventilation Syndrome: A Systematic Review of the Literature.
Basu SM, Chung FF, AbdelHakim SF, Wong J
Anesth Analg 2017 Jan;124(1):169-178. doi: 10.1213/ANE.0000000000001470. PMID: 27918326
Cardiac rhythm disturbances among children with idiopathic congenital central hypoventilation syndrome.
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
Panic disorder and agoraphobia: hypothesis hothouse.
Klein DF
J Clin Psychiatry 1996;57 Suppl 6:21-7. PMID: 8647794
Ventilatory response to exercise in children with congenital central hypoventilation syndrome.
Paton JY, Swaminathan S, Sargent CW, Hawksworth A, Keens TG
Am Rev Respir Dis 1993 May;147(5):1185-91. doi: 10.1164/ajrccm/147.5.1185. PMID: 8484629

Prognosis

Perioperative outcomes and the effects of anesthesia in congenital central hypoventilation patients.
Chang GY, Salazar T, Karnwal A, Kun SS, Ellashek J, Shin CE, McComb JG, Keens TG, Perez IA
Sleep Breath 2023 May;27(2):505-510. Epub 2022 May 13 doi: 10.1007/s11325-022-02632-z. PMID: 35554785
Impaired ventilation during 6-min walk test in congenital central hypoventilation syndrome.
Ghosh RN, Guglani L, Westbrook AL, Mao CY, Bai S, Keens TG, Kasi AS
Pediatr Pulmonol 2022 Jul;57(7):1660-1667. Epub 2022 May 5 doi: 10.1002/ppul.25940. PMID: 35460211
Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases.
Bardanzellu F, Pintus MC, Fanos V, Marcialis MA
Curr Pediatr Rev 2019;15(3):139-153. doi: 10.2174/1573396315666190621103954. PMID: 31223092
Anesthetic Considerations for Patients With Congenital Central Hypoventilation Syndrome: A Systematic Review of the Literature.
Basu SM, Chung FF, AbdelHakim SF, Wong J
Anesth Analg 2017 Jan;124(1):169-178. doi: 10.1213/ANE.0000000000001470. PMID: 27918326
Late-onset congenital central hypoventilation syndrome and a rare PHOX2B gene mutation.
Magalhães J, Madureira N, Medeiros R, Fernandes PC, Oufadem M, Amiel J, Estêvão MH, Reis MG
Sleep Breath 2015 Mar;19(1):55-60. Epub 2014 May 4 doi: 10.1007/s11325-014-0996-7. PMID: 24792884

Clinical prediction guides

Decannulation in congenital central hypoventilation syndrome.
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
Impaired ventilation during 6-min walk test in congenital central hypoventilation syndrome.
Ghosh RN, Guglani L, Westbrook AL, Mao CY, Bai S, Keens TG, Kasi AS
Pediatr Pulmonol 2022 Jul;57(7):1660-1667. Epub 2022 May 5 doi: 10.1002/ppul.25940. PMID: 35460211
Dysregulated glucose homeostasis in congenital central hypoventilation syndrome.
Musthaffa YM, Goyal V, Harris MA, Kapur N, Leger J, Harris M
J Pediatr Endocrinol Metab 2018 Dec 19;31(12):1325-1333. doi: 10.1515/jpem-2018-0086. PMID: 30447143
Anesthetic Considerations for Patients With Congenital Central Hypoventilation Syndrome: A Systematic Review of the Literature.
Basu SM, Chung FF, AbdelHakim SF, Wong J
Anesth Analg 2017 Jan;124(1):169-178. doi: 10.1213/ANE.0000000000001470. PMID: 27918326
Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children.
Charnay AJ, Antisdel-Lomaglio JE, Zelko FA, Rand CM, Le M, Gordon SC, Vitez SF, Tse JW, Brogadir CD, Nelson MN, Berry-Kravis EM, Weese-Mayer DE
Chest 2016 Mar;149(3):809-15. Epub 2016 Jan 12 doi: 10.1378/chest.15-0402. PMID: 26378991

Recent systematic reviews

Transitional care and clinical management of adolescents, young adults, and suspected new adult patients with congenital central hypoventilation syndrome.
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
Anesthetic Considerations for Patients With Congenital Central Hypoventilation Syndrome: A Systematic Review of the Literature.
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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