Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: MRI, EEG, Pupillometry.
- Who it may be relevant to
- Registry conditions: Ondine Syndrome (Congenital Central Hypoventilation Syndrome). Basic parameters: 7 years — 20 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Study of the Impact of Locus Coeruleus Dysfunction on Cognitive Function in Young Subjects With Ondine Syndrome
Overview
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.
Detailed 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."
Interventions
- Other MRI, EEG, Pupillometry
Comparison of P300 wave amplitude, pupillometric responses, functional and structural brain connectivity, socio-adaptive function, cardiac autonomic balance between two phenotypic severity groups of young patients with Ondine Syndrome.
Primary outcome measures
- Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks. [Time frame: 24 hours]
Secondary outcome measures (5)
- Ratio of maximal pupil diameter during attention tasks to resting pupil diameter measured by pupillometry. [Time frame: 24 hours]
- Functional connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging. [Time frame: 24 hours]
- Scores of socio-adaptive behavior from the Vineland neuropsychological test (Vineland Adaptative Behavior Scales II, with scores ranging from 20 to 160; higher scores indicating better functioning). [Time frame: 24 hours]
- Heart rate variability parameters from Holter ECG monitoring. [Time frame: 24 hours]
- Structural connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging. [Time frame: 24 hours]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- Robert Debré Hospital — Paris
Identifiers
NCT: NCT07081464 · APHP241606 · N° IDRCB : 2025-A00156-43