“Ondine’s curse”, also known as Congenital central hypoventilation syndrome (CCHS), is an infrequent neurological disorder. It is characterized by inadequate breathing during sleep and, in more severe cases, during waking periods.
The condition is so uncommon that it is often referred to by the tagline “You Sleep, You Die.”
The term’ Ondine’s curse’ is a nod to a German myth, where Ondine, a water nymph, curses her unfaithful husband to stop breathing if he falls asleep.
“Ondine” is a play written in 1938 by the French dramatist Jean Giraudoux. It is based on the 1811 novella “Undine” by the German Romantic writer Friedrich de la Motte Fouqué. The story focuses on the characters Hans and Ondine.
In this tale, Ondine is an immortal water spirit who becomes human after falling in love with a man, marrying him, and having a child. In one version of the story, when she discovers her husband sleeping with another woman, she curses him to remain awake, forcing him to control his breathing.
Case Report: Severinghaus and Mitchell reported the first documented case of CCHS in 1962. This case involved three patients who developed the condition after undergoing surgery on the upper cervical spinal cord and brainstem. This early documentation paved the way for further research and a better understanding of the condition.
Causes: CCHS is typically exhibited as a congenital disorder. However, acquired CHS can develop as a result of severe injury or trauma to the brain or brainstem. Other causes include brain tumours, encephalitis, poisoning, and specific neurodegenerative conditions such as Parkinson’s disease, multiple system atrophy, or multiple sclerosis.
A mutation in the PHOX2B(paired-like homeobox 2B) gene, crucial for developing neural crest cells, is the leading cause of CCHS.
Pathophysiology: is a rare disorder characterized by impaired autonomic control of breathing during sleep due to the loss of vagal input and reduced sensitivity of CO2 receptors in the medulla.
Signs & Symptoms: Sleep-dependent hypoventilation without neuromuscular, cardiac, metabolic, or pulmonary disease is the hallmark of CCHS.
Children with the ondine curse have abnormalities in cardiovascular physiology, including blood pressure control and orthostatic hypotension, diminished heart rate variability, and an attenuated increase in heart rate to exercise. Ophthalmic abnormalities (meiosis, strabismus, and convergence insufficiency) are common in children with CCHS.
Diagnosis: Children with CCHS may experience life-threatening episodes of apnea accompanied by cyanosis. Polysomnography indicates that hypoventilation is most pronounced during slow-wave sleep. The diagnosis can be confirmed through testing for mutations in the PHOX2B gene.
According to the American Thoracic Society guidelines, a mutation in the PHOX2B gene is necessary for a definitive diagnosis of CCHS.
Haddad syndrome: This is a rare genetic disorder characterized by a combination of Hirschsprung disease and congenital central hypoventilation syndrome (CCHS). The problem here also lies in the mutation of the PHOX2B gene located on chromosome 4p12.
Treatment: There is currently no cure for CCHS. Treatment focuses on managing symptoms to ensure safety and comfort. Most individuals require a tracheostomy and lifelong mechanical ventilation to survive. Diaphragm pacing is an alternative to using a mechanical ventilator. Additional treatments may include oxygen therapy and medications that stimulate the respiratory system.
Support System: Two leading organizations are dedicated to developing new treatments for CCHS. The first is “Keep Me Breathing,” a UK-based research charity focusing exclusively on CCHS. The second is “The CCHS Network,” a US-based research charity that allocates most of its funding to scientific research related to CCHS.
