Congenital central hypoventilation syndrome in children: a Hong Kong perspective

Variants in PHOX2B gene result in increased polyalanine repeat expansion mutations (PARMs) and decreased transcription of PHOX2B.18 19 Most patients with CCHS have a heterozygous in-frame PARM that encodes 24 to 33 alanines, producing genotypes 20/24 to 20/33; genotypes 20/26, 20/27, and 20/28 are predominant.7 18 19 Lower numbers of PARMs are associated with night-time ventilatory support; higher numbers of PARMs are associated with continuous ventilatory support. Children with high numbers of PARMs (genotypes 20/27 to 20/33) and children with most NPARMs may require 24-hour ventilatory support.7 Cardiovascular aspect Cardiovascular abnormalities include arrhythmias, sinus pause, sinus bradycardia, reduced heart rate variability, and prolonged R-R interval with risk of sudden death.31 Altered blood pressure can lead to nocturnal hypertension and postural hypotension, characterised by dizziness, fainting, and syncope Gastrointestinal aspect Hirschsprung disease (HD) was first described in 197832; the three affected patients died in infancy. Microphthalmia, lacrimal duct obstruction, tearing insufficiency, Marcus Gunn jaw-winking, and crocodile tears may also occur.7 Neurological and neurodevelopmental aspect Acute neurological events may be precipitated by cardiovascular, respiratory or endocrine factors.7Concerning long-term neurodevelopmental outcomes, magnetic resonance imaging of children with CCHS revealed significantly reduced grey matter volumes in autonomic, respiratory, and cognitive areas; gradual increases in grey matter were limited, consistent with age-related functional deterioration.37 Children with CCHS exhibit diverse impairments (eg, cognition, vision, language, abstract reasoning, and memory),38 39 40 along with learning disabilities and attention deficits.41 For example, preschool-age children with more severe symptoms display significantly lower motor and mental development scores on the Bayley Scales of Infant Development, indicating early onset of developmental problems42; higher numbers of PARMs are associated with lower Bayley scores. Medical examinations should exclude brain, heart, and lung lesions; they should demonstrate impaired responses to hypercapnia and hypoxia.7 Alveolar hypoventilation should be diagnosed via continuous polysomnography or cardiorespiratory polygraphy.7 19 Partial pressure of carbon dioxide (PCO2) should be monitored during multiple sleep cycles and while awake, using end-tidal CO2 or transcutaneous CO2 m