What is CCHS?
Congenital Central Hypoventilation Syndrome (CCHS; Ondine’s Curse) is a genetic condition involving the autonomic nervous system, which controls the body’s automatic functions, including breathing. It is congenital because babies appear to be born with this condition although some may not have problems immediately after birth. It is central because it involves the central nervous system, that is the brain. The breathing centres are at the base of the brain (brain stem), just above where the spinal cord enters the skull. Hypoventilation means under-breathing, and this is most serious during sleep – it is proven by measuring rises in carbon dioxide (the body’s waste gas) and falls in oxygen levels in the blood.
Problems with breathing can occur also during wakefulness, although usually to a milder degree. So the breathing disorder ranges in severity from relatively mild under-breathing during only parts of sleep and normal breathing when awake, through to a complete cessation of breathing during sleep and severe under-breathing during wakefulness – this may particularly show with feeding (particularly in infancy) or concentrating.
Why has CCHS been referred to as Ondine’s Curse?
Ondine’s Curse is an unfortunate name which was given to the condition in 1962. This name for the condition comes from a German legend in which the nymph, Ondine, placed a curse on her unfaithful mortal husband, removing all his body’s automatic functions and he therefore had to remember to breathe. When he went to sleep, he stopped breathing.
Most individuals with CCHS do not stop breathing altogether, but do not breathe deeply enough.
What causes CCHS?
In recent years, we have learnt that CCHS is due to a problem with a specific gene that affects the way nervous tissue in the brain develops early in fetal life. This abnormality is thought to arise in most cases spontaneously at the time of the formation of the new embryo, a situation known as a spontaneous mutation. All cells of the affected infant will have the abnormal gene and parents will usually be unaffected. However, we know that in 5-10% of cases, one parent may carry the genetic abnormality. These parents may have this genetic abnormality in all their body’s cells or in only some. This explains in part why some parents have been found to have hypoventilation after positive genetic testing, whereas most do not.
Differences in the gene in normal & CCHS
The genetic abnormality affects the control region, called PHOX2b, in one of a pair of genes on chromosome number 4 (there are 23 pairs of chromosomes in each cell of the body). The PHOX2b gene is responsible for development of brain tissue in the early embryo, ie before 8 weeks of pregnancy. At one point of the gene, there is a run of 20 proteins (known as nucleotides) called alanine, but the affected gene has anywhere between 25 and 33 alanines – this is called a repeat polyalanine expansion. This abnormality is not found in non-affected individuals. Thus PHOX2b has been described as a disease-defining gene. Experiments in mice have shown that if both genes are affected, the fetuses do not survive the pregnancy.
If an individual with PHOX2B has children, they have a 50% chance of passing the affected gene on. If carrying the gene, an individual will be affected to some extent or other, ie there is no silent carrier status. So we are now newly recognising some adults with the condition, in whom it was never suspected earlier in life. If an adult with PHOX2B has a child, detection of the disorder is possible in the affected fetus early in pregnancy.
How common is CCHS?
It is unknown how many children there are with CCHS. It has been estimated that the incidence is somewhere between 1 affected baby in every 50,000 – 200,000 live births, making this a very rare condition. In the larger European countries, each probably has between 50 and 100 affected individuals. There is no complete information on where children and adults with CCHS live in most countries, although a pan-European CCHS Registry is being set up, as currently exists in France.
What is affected in CCHS?
Breathing Affected individuals do not perceive and respond to changes in oxygen and carbon dioxide automatically, as would occur in unaffected individuals. This can lead to poorly inflated lungs, poor growth and development, severe pneumonia, heart strain, fits, brain injury and death. To treat this, an individual must have their breathing assisted with ventilation. This is known as mechanical ventilation. The condition is lifelong and mechanical ventilation will always be needed.
The main problem affects breathing, but any of the parts of the body under automatic control may be affected. This includes the heart, eyes, gut, brain and skin.
- face mask or nasal pillows
- phrenic nerve pacing
- negative pressure ventilation
The choice of which technique(s) are used depends on age, severity of condition and experience of treating physicians. No single method is superior.
Affected individuals do not perceive and respond to changes in oxygen and carbon dioxide automatically, as would occur in unaffected individuals. This can lead to poorly inflated lungs, poor growth and development, severe pneumonia, heart strain, fits, brain injury and death.
To treat this, an individual must have their breathing assisted with ventilation. This is known as mechanical ventilation. The condition is lifelong and mechanical ventilation will always be needed.
Individuals affected with CCHS may have pauses in heart rhythm (sinus arrest). This may present with episodes of dizziness, collapse or seizures. In some cases a cardiac pacemaker is needed. Mild cases are unlikely to have this complication.
Feeding and bowels
The nerve control to the gullet, stomach and bowels may be affected. If the large bowel is affected, this may present with severe constipation or abdominal distension (known as Hirschsprung’s disease) and requires bowel surgery. If the gullet and stomach are affected, this may be associated with indigestion, difficulty swallowing and poor appetite.
|Brain and nervous system
Some individuals may show evidence of other problems affecting the brain and development. This may show as learning difficulty, epilepsy, or vision and hearing problems. Also, blue breath holding episodes, triggered by anger, pain or fear, are more common in early life than in unaffected children.
Individuals with more severe forms of CCHS are also at risk of developing abnormal growths of nerve cells (nerve tumours) that are part of the autonomic nervous system. These can be screened for routinely.