Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome) (ONDINE-LC)

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

Conditions: Ondine Syndrome (Congenital Central Hypoventilation Syndrome)

Treatments: Other: MRI, EEG, Pupillometry

Study type: Observational

Funder types: Other

Identifiers

NCT07081464

N° IDRCB : 2025-A00156-43 (Registry Identifier)

APHP241606

Details and patient eligibility

About

This study investigates whether cognitive dysfunction in young patients with congenital central hypoventilation syndrome (Ondine Syndrome) is related to the severity of the disease and dysfunction of the locus coeruleus (a brainstem structure involved in autonomic control and cognition). The investigators will assess cognitive evoked potentials (P300 wave) using high-resolution EEG during attention tasks, pupillometry, brain MRI, neuropsychological tests, and heart rate variability. Patients with different severities of PHOX2B gene mutation (alanine expansions <27 vs. ≥27) will be compared.

Full description

Ondine Syndrome (congenital central hypoventilation syndrome) is a rare autosomal dominant genetic disorder caused by mutations in PHOX2B. Patients require lifelong nocturnal ventilation and often have cognitive impairments. The cause of cognitive deficits is uncertain: possible hypoxic brain injury or direct effects of PHOX2B mutations on brain regions like the locus coeruleus.

This cross-sectional study includes 21 patients aged 7-20 years with Ondine Syndrome and PARM-type (polyalanine repeat mutation) PHOX2B mutations, divided into moderate (<27 alanine expansions) and severe (≥27 expansions) groups. During routine hospitalization, participants undergo:

High-resolution EEG with evoked potentials during auditory and visual attention tasks to measure P300 wave amplitude.

Pupillometry during the same tasks to assess locus coeruleus function.

3T (3 Tesla magnetic resonance imaging) MRI (anatomical and diffusion imaging) without sedation.

Neuropsychological assessment with the Vineland test.

Holter ECG to analyze heart rate variability.

The goal is to link locus coeruleus dysfunction to disease severity and explore its impact on cognition, autonomic balance, and sleep."

Enrollment: 25 estimated patients

Sex: All

Ages: 7 to 20 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Neonatal diagnosis of Ondine Syndrome.
• PARM-type PHOX2B mutation.
• Age 7 to 20 years.
• Receiving nocturnal ventilation.
• Consent obtained. Affiliated with social security.

Exclusion criteria

• Severe autism spectrum disorder preventing test completion.
• Legal guardianship or curatorship.

Trial design

25 participants in 2 patient groups

Subjects with severe Ondine syndrome (PHOX2B mutation with ≥ 27 alanine expansions)

Treatment:

Other: MRI, EEG, Pupillometry

Subjects with moderate Ondine syndrome (PHOX2B mutation with < 27 alanine expansions);

Treatment:

Other: MRI, EEG, Pupillometry