Sleep Disorders in Children with Rett Syndrome
Abstract
1. Introduction
2. Genetics of Rett Syndrome
3. Sleep Disturbances in Rett Syndrome
3.1. Disturbances in Sleep Initiation and Maintenance
3.2. Abnormal Nocturnal Breathing
3.3. Other Sleep Abnormalities (Vocalizations, Abnormal Movements, Bruxism, and Nocturnal Seizures)
4. Sleep Impacts on Mental and Behavioral Health and Quality of Life
5. Sleep Measurement and Objective Findings in Rett Syndrome
6. Sleep-Directed Therapies
6.1. Disturbances in Sleep Initiation and Maintenance
6.2. Sleep-Related Movement Disorders
6.3. Sleep-Related Breathing Disorders
6.4. Additional Recommendations
Drug Name | Class or Mechanism | Common Indication | Evidence in RTT Studies | Considerations in RTT |
---|---|---|---|---|
Melatonin | Synthetic exogenous hormone; regulates circadian rhythm | Insomnia, delayed sleep phase onset | Most commonly used in RTT based on parent survey [27,28]. One randomized crossover trial showed decreased SE and increased TST [69]. | OTC, variable dosing practices |
Clonidine | α2-adrenergic agonist | FDA approved for ADHD, >6 years old; off label for insomnia, RLS: indicated for antihypertensive in adults | Often used off-label as sedative in neurodevelopmental disorders [4,28]. | Can lower blood pressure |
Trazodone | Serotonin antagonist and reuptake inhibitor | Antidepressant for adults, off-label for insomnia | Mild sedative effects; discussed in behavioral comorbidity context [28,61]. | QTc prolongation risk; priapism, limited pediatric data [63,68]; no FDA indication for pediatric patients |
Gabapentin | GABA analog | Anticonvulsant, RLS, neuropathic pain, off -label for insomnia | Occasionally used as sedative for comorbid conditions in RTT with RLS and seizures; few data specific to pediatric RTT [4]. | Sedation and mood effects should be monitored [4] |
Clonazepam, diazepam, oxazepam | Benzodiazepine; GABA-A receptor agonist | Anticonvulsant, insomnia, anxiety, muscle relaxant | Based on parent survey, for dual use as sedative and for epilepsy management [4,28]. | Dependence risk; respiratory depression in high doses [4] |
Diphenhydramine | First-generation antihistamine | Allergies, off label OTC sleep aid | Based on parent survey, used as sedating option in refractory insomnia in 1 study [28]. | Can cause paradoxical agitation; not for chronic use [28] |
Hydroxyzine | First-generation antihistamine | Sedation premedication for procedure, anxiety, pruritus (approved for pediatric use) | Based on parent survey, used for insomnia [28]. | Hypersedation, stupor, nausea, and vomiting |
Cyproheptadine | Antihistamine | Allergies, appetite stimulant | Based on parent survey, used for insomnia [28]. | Daytime sleepiness, weight gain |
Escitalopram | SSRI | Antidepressant for >12 years old, general anxiety disorder for adults | One case report shows dramatic sleep and mood improvement in RTT [75]. | Bruxism reported; dosing must be carefully titrated |
Carnitine | Amino acid and nutritional supplement | Nutritional supplement | Open-label trial with 21 subjects showing improved SE and TST [73]. | Older study and no follow up, 2001 |
Trofinetide | Synthetic analog of a naturally occurring brain peptide; insulin-like growth factor 1 [63,64] | Indicated for RTT for >2 years old; proposed mechanism of action is to promote synaptic maturation | Improved scores on RSBQ and clinical Global Impression Improvement scale. One case report with sleep improvement [59]. | No direct evidence of improved sleep |
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Harner, C.; Gaffey, T.A.; Sullivan, S.S.; Witmans, M.; DelRosso, L.M.; Tablizo, M.A. Sleep Disorders in Children with Rett Syndrome. Children 2025, 12, 869. https://doi.org/10.3390/children12070869
Harner C, Gaffey TA, Sullivan SS, Witmans M, DelRosso LM, Tablizo MA. Sleep Disorders in Children with Rett Syndrome. Children. 2025; 12(7):869. https://doi.org/10.3390/children12070869
Chicago/Turabian StyleHarner, Christopher, Thomas A. Gaffey, Shannon S. Sullivan, Manisha Witmans, Lourdes M. DelRosso, and Mary Anne Tablizo. 2025. "Sleep Disorders in Children with Rett Syndrome" Children 12, no. 7: 869. https://doi.org/10.3390/children12070869
APA StyleHarner, C., Gaffey, T. A., Sullivan, S. S., Witmans, M., DelRosso, L. M., & Tablizo, M. A. (2025). Sleep Disorders in Children with Rett Syndrome. Children, 12(7), 869. https://doi.org/10.3390/children12070869