Clinical, Sleep, and Chronobiological Characteristics of Children with Smith–Magenis Syndrome Under Treatment for Sleep Disorders.

Highlights: What are the main findings? Children with Smith–Magenis syndrome showed persistent short and poor-quality sleep despite treatment. Very high melatonin levels persisted after treatment withdrawal, suggesting possible iatrogenic accumulation in children receiving very high doses, whose mel...

Descripción completa

Detalles Bibliográficos
Publicado en:Children Vol. 12; no. 11; pp. 1471 - 1493
Autores principales: Comajuan, Marion, Guyon, Aurore, Raverot, Véronique, Babinet, Marie-Noelle, Lioret, Julien, Brunel, Lisa, Claustrat, Bruno, Demily, Caroline, Franco, Patricia
Formato: research tables/charts Journal Article
Publicado: MDPI Nov2025
Acceso en línea:Ver este registro en EBSCOhost
fields @attributes:
  recordID: 1
pdfLink:
plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=189652504&site=ehost-live
header:
  @attributes:
    shortDbName: ccm
    uiTerm: 189652504
    longDbName: CINAHL Complete
    uiTag: AN
  controlInfo:
    bkinfo:
    dissinfo:
    jinfo:
      jid:
        22279067
        LW6K
      jtl: Children
      issn: 22279067
      maglogo: N
    pubinfo:
      dt: Nov2025
      vid: 12
      iid: 11
      pid: 97109
      pub: MDPI
    artinfo:
      ui:
        189652504
        189652504
        189652504
        10.3390/children12111471
        189652504
      ppf: 1471
      ppct: 22
      formats:
      tig:
        atl: Clinical, Sleep, and Chronobiological Characteristics of Children with Smith–Magenis Syndrome Under Treatment for Sleep Disorders.
      aug:
        au:
          Comajuan, Marion
          Guyon, Aurore
          Raverot, Véronique
          Babinet, Marie-Noelle
          Lioret, Julien
          Brunel, Lisa
          Claustrat, Bruno
          Demily, Caroline
          Franco, Patricia
        affil: Service d'Epileptologie Clinique, des Troubles du Sommeil et de Neurologie Fonctionnelle de L'enfant, Hospices Civiles de Lyon, 69677 Bron, France
      sug:
        subj:
          Smith-Magenis Syndrome Symptoms
          Chronobiology Disorders Symptoms
          Sleep Disorders Drug Therapy
          Sleep
          Melatonin Therapeutic Use
          Adrenergic beta-Antagonists Therapeutic Use
          Drug Efficacy
          Human
          Male
          Female
          Child, Preschool
          Child
          Prospective Studies
          Hospitalization
          Polysomnography
          Descriptive Statistics
          Actigraphy
          Saliva Analysis
          Sleep Duration
          Wilcoxon Rank Sum Test
          Antipsychotic Agents
          Methylphenidate
          Antidepressive Agents
          Scales
          Child, Preschool: 2-5 years
          Child: 6-12 years
          Male
          Female
      ab: Highlights: What are the main findings? Children with Smith–Magenis syndrome showed persistent short and poor-quality sleep despite treatment. Very high melatonin levels persisted after treatment withdrawal, suggesting possible iatrogenic accumulation in children receiving very high doses, whose melatonin metabolism (potentially involving slow metabolizers) remains poorly understood. What are the implications of the main findings? Routine monitoring of salivary melatonin and personalized dose titration could optimize treatment, avoid overexposure, and improve both sleep and behavior. Non-pharmacological approaches such as controlled light therapy and other chronobiotic strategies may represent promising complementary or alternative options to improve circadian alignment in SMS. Background/Objectives: Smith–Magenis Syndrome (SMS) is a rare neurodevelopmental disorder characterized by severe sleep disturbances and an advanced melatonin rhythm. Current treatments, mainly exogenous melatonin and β-blockers, have not been evaluated in children. This study aimed to characterize the clinical, sleep, and chronobiological profiles of children with SMS under treatment and to assess the effects of melatonin and β-blockers. Methods: In this prospective, single-center study, 20 children with genetically confirmed SMS (aged 5–13 years; 55% female) underwent 15-day home actimetry and 48 h hospitalization, during which questionnaires, polysomnography (PSG), and salivary melatonin/cortisol profiling were performed. Melatonin and psychostimulants were discontinued 36 h before hospitalization. Results: Overall, 95% of children received melatonin and 20% β-blockers. Despite treatment, insomnia was reported in 90%, excessive daytime sleepiness in 65%, and learning problems in 90%. On actimetry, melatonin improved the mean nocturnal awakening duration (1.4 vs. 2.3 min, p = 0.040), wake-up time (06:50 vs. 06:11, p = 0.004), and longest continuous sleep episode (398 vs. 317 min, p = 0.040), but had little effect on the total sleep time, efficiency, and midpoint of sleep. Very high daytime salivary melatonin persisted (median peak 169.50 pg/mL) despite the last exogenous melatonin intake being more than 48 h prior to sampling, suggesting possible iatrogenic accumulation. The median peak in melatonin occurred at 11:57 and that in cortisol at 08:22. In children with β-blockers, there was a tendency toward an earlier melatonin peak but also toward delayed sleep onset, increased nocturnal awakenings, and reduced total sleep. Conclusions: Children with SMS showed persistent sleep difficulties and an advanced circadian phase despite sleep treatments. Exogenous melatonin provides partial benefit but may lead to daytime accumulation, while β-blockers may have adverse sleep effects despite beneficial effects on melatonin peak secretion, warranting further study.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
    refInfo:
    holdings:
      @attributes:
        islocal: N