About primary central hypoventilation syndrome

What is primary central hypoventilation syndrome?

Primary central hypoventilation syndrome is a disorder affecting normal breathing. 

  • It causes people to take shallow breaths resulting in a lack of oxygen and accumulation of carbon dioxide in the blood. 
  • The component of the nervous system that controls involuntary body processes would normally respond to such an imbalance by encouraging the person to breathe deeper or wake up.
  • People with primary central hypoventilation syndrome require mechanical ventilation or a device that stimulates a regular breathing pattern to assist them in breathing (diaphragm pacemaker). Some people who are impacted require assistance 24 hours a day, while others just require it at night.
  • The most well-known symptom of primary central hypoventilation syndrome is an inability to control breathing, which varies in severity and necessitates life-long ventilatory support in some people during sleep and all of the time in others. 
  • To avoid serious consequences caused by periods of low or no oxygen, it is critical to get a diagnosis and treatment as soon as possible.
  • Primary central hypoventilation syndrome is thought to affect between 1000 and 1200 people worldwide. Males and females are both affected by primary central hypoventilation syndrome. Affected newborns hyperventilate when falling asleep, shortly after their births.



What are the symptoms for primary central hypoventilation syndrome?

Reduced or shallow breathing is a defining feature of primary central hypoventilation syndrome, which is caused by dysregulation of the respiratory drive. Breathing abnormalities are most noticeable during non–REM sleep, but they are also present during REM sleep and awake, though to a lesser extent. 

  • When affected newborns fall asleep, they hypoventilate. A shortage of oxygen in the blood makes the skin or lips of these infants appear bluish (cyanosis). It may not show symptoms until later in life for some of the milder cases. 
  • Changes in temperature regulation, changes in heart rate variability, changes in blood pressure regulation, and poor circulation, which may only be noticeable under stressors like illness or surgery. 
  • People with primary central hypoventilation syndrome may have trouble regulating their heart rate and blood pressure, for example, in reaction to exercise or changes in body position, in addition to breathing difficulties. They also have a lower pain threshold, a lower body temperature, and profuse sweating occasionally.
  • Eye abnormalities, such as a reduced reaction of the pupils to light, are common in people with primary central hypoventilation syndrome. People may have a distinctive appearance with a small, wide, slightly flattened face that has been dubbed "box-shaped."



What are the causes for primary central hypoventilation syndrome?

Primary central hypoventilation syndrome is caused by mutations in the PHOX2B gene. 

  • PHOX2B is a gene that gives instructions for manufacturing a protein that is crucial for development before birth. PHOX2B is a protein that aids in the creation of nerve cells. 
  • Primary central hypoventilation syndrome is a dominant genetic disorder, which means that just one PHOX2B gene mutation is required for its phenotypic presentation. The majority of the instances are spontaneous, even though most genetic illnesses are passed from parents.
  • The neural crest, a collection of cells in the early embryo that gives rise to a lot of tissues and organs, is where the protein is active. Neural crest cells migrate to build the autonomic nervous system, a variety of tissues in the face as well as the skull, and a variety of other tissues and cell types.
  • PHOX2B controls the maturation of neurons to perform certain roles like differentiation. Although mosaic parents have been found in the CCHS population, they are still extremely rare.
  • Genetic counseling is recommended for parents who want to have more children after having a child with primary central hypoventilation syndrome. PHOX2B mutations are stable from down the generations, but penetrance and phenotype can still differ dramatically.



What are the treatments for primary central hypoventilation syndrome?

The goal of treatment for primary central hypoventilation syndrome is to provide breathing assistance, which is usually accomplished with the use of a respirator or ventilator. 

  • Some children with primary central hypoventilation syndrome will require a ventilator 24 hours a day, while others may just require breathing assistance when sleeping. 
  • To survive, most people require a tracheostomy and continuous artificial ventilation via a ventilator. However, it has since been demonstrated that biphasic cuirass ventilation may be used successfully without a tracheotomy. A surgical implant in the diaphragm muscles allows for electrical stimulation of the muscle.
  • Surgical implants also control breathing in some people. Oxygen therapy and medicines that stimulate the respiratory system are two other possible treatments for primary central hypoventilation syndrome. Extensive usage of ventilators is currently causing difficulties, such as deadly infections and pneumonia. 
  • Diaphragm pacing can be used involving a surgical procedure that implants two electrodes on the phrenic nerves in the thorax and two radio receivers beneath the skin. The diaphragm contracts when the phrenic nerves are stimulated electrically. The diaphragm relaxes and passive exhalation begins when the external transmitter ceases providing impulses.
  • Mechanical ventilation is required for primary central hypoventilation syndrome patients as they age.



What are the risk factors for primary central hypoventilation syndrome?

Primary central hypoventilation syndrome, if left untreated, can lead to life-threatening complications, even death. Primary central hypoventilation syndrome can lead to pulmonary hypertension, which can lead to right-sided heart failure.

  • Most children have tracheostomies when they are just a few months old. Patients with primary central hypoventilation syndrome can live productive lives, but they must rely on mechanical breathing for the rest of their lives.
  • According to recent advancements in various research, drug interventions may be possible and are not far down the pipeline. A lot of networks have been researching this potential therapy option.
  • Patients with a tracheostomy can use a specific adaptor called a "speaking valve" over the tracheotomy to speak during spontaneous breathing. To communicate, some patients simply cover their tracheostomy tubes with a cap. They can speak during mechanical ventilation. 
  • Such patients may have several coexisting diseases that necessitate medication and/or treatment. On an individual/per case basis, a patient must work closely with his or her physician to appropriately diagnose and select therapy alternatives.
  • There is no such thing as a "best" ventilatory approach. Each strategy has advantages and disadvantages. The ventilation strategy must be set by a professional center based on the age of the patient, severity of the disease, parents' preferences, and the patient's demands.



Is there a cure/medications for primary central hypoventilation syndrome?

Currently, there are no drugs for primary central hypoventilation syndrome. Treatments include:

1) Oxygen Treatment

Treatment is aimed at providing breathing assistance, typically with the use of a respirator or ventilator. Several kids with CHS will require a ventilation system 24 hours a day, while others may only require breathing assistance while sleeping.

A surgical implant in the diaphragm muscle can allow electrical stimulation of the muscle to control breathing in some people.

2) Assistance with ventilation

All patients with primary central hypoventilation syndrome will require assisted ventilation, with diaphragmatic pacing as an option for those who require 24-hour ventilation.

3) Pacing the diaphragm

Diaphragm pacing can boost your respiration and possibly eliminate your need for a mechanical ventilator.

Diaphragm pacing involves electrically stimulating your diaphragm muscles and nerves with a lightweight, battery-powered system. This provokes your diaphragm to contract, allowing air to enter your lungs. It allows you to breathe more normally.

Diaphragm pacing entails inserting four electrodes into your diaphragm muscle and a fifth electrode near the other electrodes just below the skin. After that, the electrodes are linked to an external stimulator.

The stimulator sends electrical impulses to the electrodes on a continuous basis, causing your diaphragm to contract and assisting you in breathing.

List of Symptoms

  1. Breathing difficulty
  2. A lack of oxygen in the blood often results in bluish skin or lips, as well as difficulty regulating their heart rate and blood pressure
  3. Heavy sweating occurs on occasion

List of Conditions

  1. Poor or complete lack of spontaneous breathing, particularly during sleep 
  2. Abnormal pupils
  3. Acid reflux and decreased intestinal motility make feeding difficult.
  4. Absence or deterioration of bowel function (Hirschsprung's disease)

List of Drugs

  1. Currently there are no drugs for central hypoventilation syndrome. 
  2. Most children are given tracheostomies when they are only a few months old
  3. While the patients have the potential to live productive lives, they are dependent on mechanical ventilation for the rest of their lives



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