November 12 is congenital central hypoventilation syndrome world day, also know as Ondine syndrome. It is a rare genetic disease described for the first time in 1970. The name of Ondine syndrome comes from an ancient Germanic legend about the story of this nymph and her curse on her treacherous husband: “As long as you are awake, you can have your breath, but should you ever fall asleep, then it will be taken from you and you will die!”. In fact, patients with this disorder have hypoventilation, i.e. they do not breathe adequately during sleep, so that the oxygen values in the blood drop and those of carbon dioxide rise. The problem is not borne by the lung, but depends on the brain which “forgets” to send the command to breathe and this is why the syndrome is called central.
At Bambino Gesù, the Simple Operational Unit of Semi-intensive Respiratory Therapy takes care of the children and young people affected by this syndrome, part of the Complex Operational Unit of Broncho-pneumology, the hospital’s reference structure for highly complex care cases, linked to respiratory problems. These are children and young people often dependent on mechanical ventilation, who have greater care needs than those provided in General or specialist Pediatrics wards, but fewer than in Intensive Care Units. Here is the interview with Dr. Maria Giovanna Paglietti, head of Semi-intensive Respiratory Therapy.
How many online patients are currently followed by Bambino Gesù? How many cases are there in Italy?
There are 40 patients with Congenital Central Hypoventilation or Ordine’s Syndrome followed up at our Hospital and they represent about half of the patients diagnosed in Italy.
How do they get to you? What is the path that leads them to Bambino Gesù?
They arrive from other Centres from all over Italy, mainly from Central-Southern Italy, due to symptoms such as apnea, cyanosis, respiratory failure, which cannot be explained and are difficult to treat as they appear very early. The diagnosis is often made at our Hospital. If, on the other hand, the diagnosis is made at another treatment centre, we are contacted as a clinical reference center to take care of these patients and then organize the transfer.
Once they come to us, is there a specific diagnostic and assistance path?
When a child has ventilatory insufficiency at birth, the diagnosis must be made through an accurate medical history, a careful physical examination, functional tests and genetic examination. When at the end of the process it occurs that the child has central apneas in sleep, with high carbon dioxide values and lower than normal oxygen values in the blood, a diagnosis of central hypoventilation is made. At this point, the study of the PHOX2B gene is carried out in the medical genetics laboratory directed by Prof. Antonio Novelli, the mutation of which is indicative of disease. In most cases, gene mutations arise de novo during embryogenesis, but are sometimes inherited from parents with an attenuated and often asymptomatic form of the disease. Knowing the type of mutation is very important because the clinical expression of the disease and its association with intestinal or oncological pathologies depend on it.
What does this path involve?
In the Lazio Region at the moment there is no PDTA (Diagnostic Therapeutic Assistance Pathways) for the pathology, but we follow a protocol based on the indications of the literature and clinical experience, which addresses the study of sleep and gaseous exchange, necessary to verify the effectiveness of mechanical ventilation, imaging and functional examinations of other organs and systems in order to exclude comorbidities. It is always very important to re-evaluate the psychological aspect of the patient and family at each check-up, to support each stage of growth with a chronic disease.
What is the standard treatment for this pathology? What are their life expectancies and what is the level of quality of life.
The only therapy for hypoventilation is sleep mechanical ventilation, which can be done through a tracheostomy or mask; the choice must be identified on the basis of the patient’s clinical and genetic characteristics, always jointly with the family. There is currently no medical therapy for this disease. Patients can have a long and fulfilling life, especially if they are free from comorbidities.
Bambino Gesù is part of the European network of rare lung disease (Ern Lung). Are there any ongoing research or trials that patients can be entered at this time?
There are currently several research groups on the PHOX2B gene and Congenital Central Hypoventilation. In particular, the Hospital collaborates closely in Italy with the group of Professor Ceccherini of Gaslini in Genoa and that of Professor Fornasari of the University of Milan. Some patients followed up at our Hospital have given their consent to supply biological material for ongoing pharmacological research. Our Hospital is a clinical reference center for patients and in this sense we have published our 20-year case history and the changes in clinical management that have occurred during this period in Frontiers in Pediatrics.
November 12 is World Ondine Syndrome Day. What message do you feel you can send to families experiencing this condition? What is the role and importance of patient associations?
Ondine’s syndrome is a rare and very complex pathology, which however can allow patients to have a good quality of life if they carry out precise clinical and functional checks. The message for patients is therefore to constantly carry out mechanical ventilation and regular multidisciplinary follow-up in the center where they are followed up. If the progress of medicine and technology allows patients to have increasingly performing ventilators and ever softer and more practical masks, the control of vital parameters during ventilation remains the responsibility of the parents, with many hours of sleep lost. Our thanks and our support go to them.
In Italy there is the Italian Association for Congenital Central Hypoventilation Syndrome (AISICC), born in Florence in 2003, to which most of the Italian families of the patients belong. With the monthly newsletter and the annual conference, it allows the families of patients to create a network of support and constant information. It is also valuable for pathology specialists who meet for the purpose of updating scientific research and collecting projects, often financed by the Association itself.