Systemic oxidative stress in congenital central hypoventilation syndrome

Extract

Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is a rare disorder characterised by severe hypoventilation during sleep and autonomic dysregulation [1, 2]. The incidence of CCHS is about one in 200 000 live births. In >90% of cases, polyalanine repeat expansion mutations are present in the paired-like homeobox PHOX2B gene, although a frameshift variant may also be found [3]. The PHOX2B gene encodes a highly conserved homeobox domain transcription factor that plays a regulatory role in the differentiation of the motor neuron and the serotonergic neuronal fate in the development of the central nervous system [4]. The hallmark of CCHS is the “forgotten breathing”, which implies the need for life-long mechanical ventilation during sleep. However, in more severe cases characterised by global hypoventilation, mechanical ventilation must also be extended during wakefulness. Ventilatory support may be provided by tracheostomy and assisted ventilation, noninvasive ventilation or diaphragm pacemakers. Severe respiratory depression typically arises at birth but in milder cases, CCHS may be diagnosed later on in childhood or adulthood (later-onset CCHS) [1, 2].