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Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction(CCHS2)

MedGen UID:
1794173
Concept ID:
C5561963
Disease or Syndrome
Synonyms: CCHS2; CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL, 2, AND AUTONOMIC DYSFUNCTION
 
Gene (location): MYO1H (12q24.11)
 
Monarch Initiative: MONDO:0030537
OMIM®: 619482

Definition

Congenital central hypoventilation syndrome-2 and autonomic dysfunction (CCHS2) is an autosomal recessive disorder characterized by shallow breathing and apneic spells apparent in the neonatal period. Affected infants require mechanical ventilation due to impaired ventilatory response to hypercapnia, as well as tube feeding due to poor swallowing, aspiration, and gastrointestinal dysmotility. Some patients have other features of autonomic dysfunction, including bladder dysfunction, sinus bradycardia, and temperature dysregulation. Although mild global developmental delay with learning difficulties and seizures were present in the single family reported, it was unclear if these features were related to the hypoventilation phenotype (Spielmann et al., 2017). For a discussion of genetic heterogeneity of CCHS, see CCHS1 (209880). [from OMIM]

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Sinus bradycardia
MedGen UID:
39316
Concept ID:
C0085610
Pathologic Function
Bradycardia related to a mean resting sinus rate of less than 50 beats per minute.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Achalasia
MedGen UID:
5023
Concept ID:
C0014848
Disease or Syndrome
A disorder of esophageal motility characterized by the inability of the lower esophageal sphincter to relax during swallowing and by inadequate or lacking peristalsis in the lower half of the body of the esophagus.
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.
Small intestinal dysmotility
MedGen UID:
576812
Concept ID:
C0345200
Congenital Abnormality
Abnormal small intestinal contractions, such as spasms and intestinal paralysis related to the loss of the ability of the gut to coordinate muscular activity because of endogenous or exogenous causes.
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.
Gastrostomy tube feeding in infancy
MedGen UID:
892362
Concept ID:
C4023342
Finding
Feeding problem necessitating gastrostomy tube feeding.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Ineffective esophageal peristalsis
MedGen UID:
1638022
Concept ID:
C4703577
Finding
Reduced or inadequate esophageal peristalsis, with resultant slow passage of contents through the esophagus.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Hypopnea
MedGen UID:
536410
Concept ID:
C0235546
Finding
Hypopnea is referring to breathing that is abnormally shallow.
Hypoventilation
MedGen UID:
469022
Concept ID:
C3203358
Pathologic Function
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Aspiration pneumonia
MedGen UID:
10814
Concept ID:
C0032290
Disease or Syndrome
Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract.
Temperature instability
MedGen UID:
329973
Concept ID:
C1820737
Finding
Disordered thermoregulation characterized by an impaired ability to maintain a balance between heat production and heat loss, with resulting instability of body temperature.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

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

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Dudoignon B, Bokov P, Couque N, Denjoy I, Matrot B, Delclaux C
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Boulanger-Scemama E, Fardeau C, Straus C, Simon C, Touitou V, Touhami S, Amini M, Similowski T, LeHoang P
Ophthalmic Genet 2014 Dec;35(4):229-34. Epub 2014 Aug 12 doi: 10.3109/13816810.2014.946056. PMID: 25113442
Amiel J, Dubreuil V, Ramanantsoa N, Fortin G, Gallego J, Brunet JF, Goridis C
Respir Physiol Neurobiol 2009 Aug 31;168(1-2):125-32. Epub 2009 Mar 21 doi: 10.1016/j.resp.2009.03.005. PMID: 19712905

Diagnosis

Castro C, Correia C, Martins T, Portela A
BMJ Case Rep 2021 Sep 20;14(9) doi: 10.1136/bcr-2021-244679. PMID: 34544712Free PMC Article
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
Sandoval RL, Zaconeta CM, Margotto PR, Cardoso MT, França EM, Medina CT, Canó TM, Faria AS
Rev Paul Pediatr 2016 Sep;34(3):374-8. Epub 2016 Jan 6 doi: 10.1016/j.rpped.2015.10.009. PMID: 26838603Free PMC Article
Boulanger-Scemama E, Fardeau C, Straus C, Simon C, Touitou V, Touhami S, Amini M, Similowski T, LeHoang P
Ophthalmic Genet 2014 Dec;35(4):229-34. Epub 2014 Aug 12 doi: 10.3109/13816810.2014.946056. PMID: 25113442
Crowell BA, Bissinger RL, Conway-Orgel M
Adv Neonatal Care 2011 Jun;11(3):167-72. doi: 10.1097/ANC.0b013e31821cfe26. PMID: 21730909

Prognosis

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
Boulanger-Scemama E, Fardeau C, Straus C, Simon C, Touitou V, Touhami S, Amini M, Similowski T, LeHoang P
Ophthalmic Genet 2014 Dec;35(4):229-34. Epub 2014 Aug 12 doi: 10.3109/13816810.2014.946056. PMID: 25113442
Hammel M, Klein M, Trips T, Priessmann H, Ankermann T, Holzinger A
Klin Padiatr 2009 Sep;221(5):286-9. Epub 2009 Aug 25 doi: 10.1055/s-0029-1220941. PMID: 19707990
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Clinical prediction guides

Amer-Sarsour F, Falik D, Berdichevsky Y, Kordonsky A, Eid S, Rabinski T, Ishtayeh H, Cohen-Adiv S, Braverman I, Blumen SC, Laviv T, Prag G, Vatine GD, Ashkenazi A
EMBO J 2024 Jan;43(2):250-276. Epub 2024 Jan 2 doi: 10.1038/s44318-023-00018-9. PMID: 38177505Free PMC Article
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
Zelko FA, Stewart TM, Brogadir CD, Rand CM, Weese-Mayer DE
Pediatr Pulmonol 2018 Apr;53(4):492-497. Epub 2018 Jan 12 doi: 10.1002/ppul.23939. PMID: 29327497
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Gaultier C, Trang H, Dauger S, Gallego J
Pediatr Res 2005 Jul;58(1):1-6. Epub 2005 May 18 doi: 10.1203/01.PDR.0000166755.29277.C4. PMID: 15901893

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