Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
Conditions
Keywords
Locus Coeruleus, PHOX2B, Cognitive Dysfunction, EEG, Pupillometry, MRI, Ondine Syndrome
Brief summary
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
OTHERMRI, 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.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
7 Years to 20 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amplitude of the P300 wave (peak-to-baseline) recorded by high-resolution EEG during visual and auditory attention tasks. | 24 hours | Measurement of cognitive evoked potential P300 amplitude using a 64-electrode EEG system during Flanker and oddball paradigms to assess locus coeruleus function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of maximal pupil diameter during attention tasks to resting pupil diameter measured by pupillometry. | 24 hours | — |
| Functional connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging. | 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). | 24 hours | Vineland Adaptative Behavior Scales II, with scores ranging from 20 to 160; higher scores indicating better functioning. |
| Heart rate variability parameters from Holter ECG monitoring. | 24 hours | — |
| Structural connectivity parameters of the locus coeruleus measured by high-resolution EEG and 3T brain MRI diffusion imaging. | 24 hours | — |
Countries
France
Contacts
Primary ContactFrançois-Xavier MAUVAIS, MD, PhD
Backup ContactChristophe DELCLAUX, MD, PhD
Outcome results
None listed