central hypoventilation syndrome; primary alveolar hypoventilation; Ondine's curse

Etiology

• congenital (most common)
• brainstem infarction

Epidemiology

• rare
• no gender predilection

Pathology

• deficiency in autonomic control of respiration results in inadequate or negligible ventilatory & arousal responses to hypercapnia & hypoxemia
• other neurocristopathies:
  • neuroblastoma, Hirschsprung disease (16%)
• dysphagia may occur with brainstem infarction

Genetics

• mutations in PHOX2B (91%)
• most mutations consist of 5-10 Ala expansions in the poly-Ala region from amino acids 241-260
• associated with defects in RET
• associated with defects in BDNF
• associated with defects in EDN3
• associated with defects in GDNF

Clinical manifestations

• variations in severity
• patients are often able to maintain rhythmic, but suboptimal respirations when awake
• during sleep, patients develop further deterioration in ventilation with frequent episodes of central hypopnea or central sleep apnea
• most patients do not survive infancy

Diagnostic procedures

• polysomnography:
  • hypoventilation most marked during slow-wave sleep

Complications

• respiratory arrest during sleep
• fatal if untreated

Management

• avoid opiates & sedatives (respiratory depression)
• ventilatory assistance during sleep
  • mechanical ventilation
    • biphasic cuirass ventilation
  • phrenic nerve pacing/diaphragm pacing

More general terms

• syndrome
• hypoventilation
• central sleep apnea

More specific terms

• congenital central hypoventilation syndrome; congenital failure of autonomic control; congenital Ondine curse (CCHS)

Additional terms

• sleep apnea