The CCHS study is a prospective, open-label, monocentric, interventional study with diagnostic and prognostic objectives, conducted in two phases. The first phase aims to identify biomarkers and dysregulated biological pathways in patients with Congenital Central Hypoventilation Syndrome (CCHS) by analyzing blood and urine samples of patients and matched healthy controls collected at multiple timepoints during sleep and wakefulness. In the second phase, these candidate biomarkers and pathways will be validated in a larger cohort of patients and matched healthy controls using targeted assays such as RT-PCR and mass spectrometry-based metabolomic analysis. The primary objective is to uncover molecular signatures that could explain disease mechanisms, while the secondary objective is to explore potential biomarkers and treatment targets that can improve spontaneous breathing and CO₂ responsiveness in CCHS patients. The underlying hypothesis is that multi-omics profiling of blood and urine can reveal actionable insights into the pathophysiology of CCHS and support the development of targeted interventions.

Inclusion Criteria:

CCHS patients :

1. Age 18 years old or older;
2. Carry a polyA expansion mutation in PHOX2B;
3. Receive nocturnal mechanical ventilation;
4. Patients that are under the care and treatment in the CCHS center: Hôpital Universitaire Pitié-Salpêtrière
5. Written informed consent from the patient
6. Affiliated to The French social security except patient on AME (state medical aid)

Control group :

1. Age 18 years old or older.
2. Healthy with no major medical illnesses in the past year (such as diabetes, cancer, pregnancy, lungs disease).
3. Matched for sex, age (+/- 3 years), origin and BMI category with a CCHS patient
4. Written informed consent of the control
5. Affiliated to The French social security except patient on AME (state medical aid)

Exclusion Criteria:

CCHS patients :

1. Age lower than 18 years old;
2. Pregnancy or breastfeeding
3. Patients with diaphragmatic (phrenic nerve) pacing;
4. Patients with late onset CCHS;
5. Patients that were diagnosed with a major medical illnesses/condition other than CCHS in the past year (such as diabetes, cancer, lungs disease, a sleep disorder, or pregnancy)
6. Patients that suffer from a sleep disorder such as insomnia, restless legs syndrome, nightmares
7. Patients who use medications that are likely to impair sleep structure
8. Individuals under guardianship, or permanently legally incompetent adults, under judicial protection, deprived of liberty, patients unable to express their consent.

Control group :

1. Age lower than 18 years old;
2. Pregnancy or breastfeeding
3. Controls that were diagnosed with a major medical illnesses/condition in the past year (such as diabetes, cancer, lungs disease, a sleep disorder, or pregnancy)
4. Controls that suffer from a sleep disorder such as insomnia, restless legs syndrome, nightmares
5. Controls who use medications that are likely to impair sleep structure.
6. Individuals under guardianship, or permanently legally incompetent adults, under judicial protection, deprived of liberty, patients unable to express their consent.

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor.

Researchers who provide a methodologically sound proposal.