Smith Magenis Syndrome Study

Study Overview
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Brief Summary
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Smith Magenis Syndrome (SMS) is a complex disorder characterized by severe neurological, psychological and behavioral disorders including sleep-wake rhythm disorders. It is a rare disease with a prevalence of 1/25 000. The sleep disorders observed could be the consequence of a general dysregulation of the circadian system, since these patients show an inversion of the melatonin secretion profile. In SMS, the peak of melatonin is observed at 12 o'clock, whereas it is nocturnal in healthy subjects (3-4 o'clock in the morning). Daylight plays a important role in circadian regulation by inducing an inhibition of melatonin secretion via the suprachiasmatic nuclei of the hypothalamus. This mechanism could be affected in SMS children, explaining the lag of melatonin profile. These sleep-wake disturbances cycle could play a significant role in learning deficits and in the frequency and severity of behavioral abnormalities observed in SMS. In this project, investigators propose to study the mechanisms involved in the sleep-wake cycle disorders observed in Smith Magenis children, in particular by evaluating the quality of the pupillary reflex using a pupillometer. The pupillary reflex is a simple and non-invasive method to test light sensitivity and the photobiological mechanisms involved. In this way, investigators want to evaluate the diurnal profile of the pupillary reflex in children with Smith Magenis syndrome in relation to the diurnal melatonin profile. Investigators will complete this study by determining the chronobiological profile of Smith Magenis patients by measuring different variables: Diurnal cortisol and amylase profile 24h body temperature and heart rate profile Urinary cortisol and 6-sulfatoxymelatonin (major metabolite of melatonin) profiles Daytime sleepiness profile measured subjectively by questionnaire and objectively via a waking EEG recording. Actimetry at home Polysomnography A neurocognitive and behavioural assessment

Official Title
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Chronobiological Characterization of Smith Magenis Syndrome in Paediatric Age

Conditions
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Smith-Magenis Syndrome

Intervention / Treatment
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* Other: Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetically confirmed Smith Magenis syndrome (microdeletion of the short arm of chromosome 17 or mutation of the RAI1 gene; obtained by FISH, CGH-array or molecular biology) Aged 7-12 years Consent form signed by the parent(s) Requiring a sleep assessment in the Hopital Femme Mère Enfant paediatric sleep unit of Pr Franco Affiliation to a social security system. Exclusion Criteria: Associated ophthalmological disorders that do not allow the photomotor reflex to be studied: optic neuritis, glaucoma and retinitis pigmentosa. Dyschromatopsia detected in consultation with a rapid Ishihara test adapted to the child's cognitive level, if necessary supplemented by a test performed by ophthalmologists. Algic child (risk of measurement bias: when a patient is in pain his pupils dilate and we observe a greater amplitude in the photomotor reflex), defined by a score on the FPS-R Face Scale >4/10.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Children with Smith Magenis Syndrome<br> | Other: Assessment<br>* Pupil reflex and melatonin profile, circadian profile assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the percentage change between pupil diameter at the end of light exposure and before exposure | This measurement will allow to evaluate the diurnal profile of the pupillary reflex and will be measured by a NeuroLight pupillometer (IDMed). This measurement will be done every 2 hours from 8am to 8pm, for one day | One day | 
| Measurement of salivary melatonin levels | This measurement will allow to evaluate the diurnal melatonin profile and will be evaluated using saliva samples. This measurement will be done every 2 hours from 8am to 8pm, for one day | One day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the chronobiological profile : Salivary cortisol levels | Salivary cortisol levels will be evaluated using saliva samples | Every 2 hours from 8am to 8pm, for one day | 
| Determination of the chronobiological profile : Amylase levels | Amylase levels will be evaluated using saliva samples | Every 2 hours from 8am to 8pm, for one day | 
| Determination of the chronobiological profile : Urinary 6-sulfatoxymelatonin level | Urinary 6-sulfatoxymelatonin level will be evaluated using urinary samples | over 24hours | 
| Determination of the chronobiological profile : Urinary cortisol level | Urinary cortisol level will be evaluated using urinary samples | over 24hours | 
| Determination of the chronobiological profile : Variations in body temperature in degrees | Body temperature will be measured by ibuttonR placed on the surface of the skin | over 24hours | 
| Determination of the chronobiological profile : Assessment of sleepiness by questionnaire (numerical score) | The Karolinska questionnaire will be carried out at the time of salivary sampling and pupil diameter measurement and the score obtained will be compared with the salivary melatonin level. | Every 2 hours from 8am to 8pm, for one day | 
| Determination of the chronobiological profile : Assessment of sleepiness by spectral analysis (EEG) | Somnolence will be evaluated by calculating power spectrum in several frequency bands. | Every 2 hours from 8am to 8pm, for one day | 
| Determination of the chronobiological profile : Sleep assessment by actimetry | Home activity monitor during an outpatient recording with a watch in order to assess the sleep wake rhythm at home | 2 weeks | 
| Determination of the chronobiological profile :Sleep assessment by Polysomnography | Polysomnography during hospitalization in order to assess the structure of sleep | 24 hours | 
| Neuropsychological assessment | WISC +/- Vineland | One day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep disorders, Chronobiology, Smith Magenis Syndrome, Paediatrics, Pupillary reflex, Circadian rhythm, Melatonin