Abnormal auditory pathways in PHOX2B mutation positive congenital central hypoventilation syndrome

Trang, Ha; Zada, Tarif Masri; Heraut, Fawzia

doi:10.1186/s12883-015-0299-z

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…Additionally, dysfunc tions of brainstem auditory pathways have been observed in infants with CCHS 13) . However, the relationship between these variable abnormal clinical features and mutations in the PHOX2B gene has not yet been identified.…”

Section: Results Of Genetic Analysis Of the Phox2b Genementioning

confidence: 99%

Haddad Syndrome with a Germ-Line Mutation in thePHOX2BGene in a Korean Neonate

et al. 2015

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Congenital central hypoventilation syndrome (CCHS) is a life-threatening disease that primarily manifests as sleep-associated respiratory insufficiency and a markedly impaired ventilatory response to hypercarbia and hypoxemia. Paired-like homeobox 2b (PHOX2B) gene mutations are known to cause CCHS. Almost all patients with CCHS are heterozygous for a poly-alanine expansion in PHOX2B. However, some patients have other germ-line abnormalities, including missense, nonsense and frame shift mutations. CCHS combined with Hirschsprung disease (Haddad syndrome) is extremely rare. Here, we report the case of a 1-day-old male neonate with recurrent apnea and bowel distension. Genetic analysis showed that he was heterozygous for a germ-line mutation in the PHOX2B gene. Only three cases of CCHS including two with Haddad syndrome confirmed by PHOX2B gene mutations have been reported in Korea. All of these cases have been heterozygous for a poly-alanine expansion mutation. This is the first report describing Haddad syndrome with a germ-line mutation in the PHOX2B gene in a Korean neonate.

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Section: Results Of Genetic Analysis Of the Phox2b Genementioning

confidence: 99%

Haddad Syndrome with a Germ-Line Mutation in thePHOX2BGene in a Korean Neonate

et al. 2015

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“…The neuronal system responsible for awakening could be impaired in CCHS patients, as a result of either mutation-related effects altering the circadian rhythm 14 or repeated hypoxic episodes. 15 , 16 The brainstem dysfunction described in CCHS patients 17 could also contribute to reduce the ability of the brain to manage the awakening process. More simply, chronically sleeping on mechanical ventilation could induce habituation to sensory stimuli (noise, leaks, alarms, tidal pressure variations) with concomitant elevation of the awakening threshold.…”

Section: Discussionmentioning

confidence: 99%

Awakening efficacy of a vibrotactile device in patients on home nocturnal ventilatory assistance and healthy subjects as family caregiver proxies

et al. 2020

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The objective of this study was to test the capacity of vibrotactile stimulation transmitted to the wrist bones by a vibrating wristband to awaken healthy individuals and patients requiring home mechanical ventilation during sleep. Healthy subjects (n = 20) and patients with central hypoventilation (CH) (Congenital Central Hypoventilation syndrome n = 7; non-genetic form of CH n = 1) or chronic obstructive pulmonary disease (COPD) (n = 9), underwent a full-night polysomnography while wearing the wristband. Vibrotactile alarms were triggered five times during the night at random intervals. Electroencephalographic (EEG), clinical (trunk lift) and cognitive (record the time on a sheet of paper) arousals were recorded. Cognitive arousals were observed for 94% of the alarms in the healthy group and for 66% and 63% of subjects in the CH and COPD groups, respectively (p < 0.01). The percentage of participants experiencing cognitive arousals for all alarms, was 72% for healthy subjects, 37.5% for CH patients and 33% for COPD patients (ns) (94%, 50% and 44% for clinical arousals (p < 0.01) and 100%, 63% and 44% for EEG arousals (p < 0.01)). Device acceptance was good in the majority of cases, with the exception of one CH patient and eight healthy participants. In summary this study shows that a vibrotactile stimulus is effective to induce awakenings in healthy subjects, but is less effective in patients, supporting the notion that a vibrotactile stimulus could be an effective backup to a home mechanical ventilator audio alarm for healthy family caregivers.

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“…Alternatively, patients with CCHS could be more isolated from noises and external disturbances that prolong sleep onset latency. In this respect, children with CCHS have a dysfunction of brainstem auditory pathways [18], which may contribute to “sensory isolation” during sleep and reduce the ability of the brain to monitor signals despite their possibly vital importance (e.g., ability to detect ventilator alarms). However, this speculative interpretation is not supported by a lower arousal index in patients with CCHS.…”

Section: Discussionmentioning

confidence: 99%

Normal sleep on mechanical ventilation in adult patients with congenital central alveolar hypoventilation (Ondine’s curse syndrome)

Attali

Straus

Pottier

et al. 2017

Orphanet J Rare Dis

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BackgroundThe purpose of this study was to describe the sleep structure (especially slow wave sleep) in adults with congenital central hypoventilation syndrome (CCHS), a rare genetic disease due to mutations in the PHOX2B gene. Fourteen patients aged 23 (19.0; 24.8) years old (median [1rst-3rd quartiles]) with CCHS underwent a sleep interview and night-time attended polysomnography with their ventilatory support. Their sleep variables were compared to those collected in 15 healthy control subjects matched for age, sex and body mass index.ResultsThe latency to N3 sleep was shorter in patients (26.3 min [24.0; 30.1]) than in controls (49.5 min [34.3; 66.9]; P = 0.005), and sleep onset latency tended to be shorter in patients (14.0 min [7.0; 20.5]) than in controls (33.0 min [18.0; 49.0]; P = 0.052). Total sleep time, sleep stage percentages, sleep fragmentation as well as respiratory and movement index were within normal ranges and not different between groups.ConclusionsNormal sleep in adult patients with CCHS and adequate ventilator support indicates that the PHOX2 gene mutations do not affect brain sleep networks. Consequently, any complaint of disrupted sleep should prompt clinicians to look for the usual causes of sleep disorders, primarily inadequate mechanical ventilation. Shorter N3 latency may indicate a higher need for slow wave sleep, to compensate for the abnormal respiratory-related cortical activity during awake quiet breathing observed in patients with CCH.

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Abnormal auditory pathways in PHOX2B mutation positive congenital central hypoventilation syndrome

Cited by 6 publications

References 21 publications

Haddad Syndrome with a Germ-Line Mutation in thePHOX2BGene in a Korean Neonate

Haddad Syndrome with a Germ-Line Mutation in thePHOX2BGene in a Korean Neonate

Awakening efficacy of a vibrotactile device in patients on home nocturnal ventilatory assistance and healthy subjects as family caregiver proxies

Normal sleep on mechanical ventilation in adult patients with congenital central alveolar hypoventilation (Ondine’s curse syndrome)

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