Key points:

1. Prevalence and Onset:

   • Sleep problems affect 70–80% of individuals with RTT, with onset becoming evident between 18 months and 2 years.
   • Sleep disturbances in RTT are significantly more common than in typically developing children.

2. Sleep Patterns:

   • Individuals with RTT often exhibit prolonged daytime naps and reduced night-time sleep.
   • Sleep issues include insomnia, frequent night awakenings, irregular sleep‒wake cycles, and circadian rhythm disturbances.
   • Night-time laughter, parasomnias, and nocturnal seizures are notable, with patterns influenced by the type of MECP2 mutation.

3. Sleep Architecture:

   • Abnormalities in both REM and NREM sleep are seen.
   • EEG characteristics include slowing, epileptiform activity, and loss of sleep spindles and K-complexes after 2 years of age.

4. Impact on Families:

   • Sleep problems disrupt not only the individual but also their families and caregivers, necessitating multidisciplinary support.

5. Pathophysiology:

   • Dysfunction in aminergic neurons, particularly the raphe nuclei and locus coeruleus, underpins the sleep‒wake rhythm disturbances.
   • Autonomic dysregulation contributes to respiratory issues like apnea, bradycardia, and hypoventilation during sleep.

Evaluation of Sleep Problems in RTT:

1. Clinical Assessment:

   • Comprehensive sleep history and documentation via a sleep diary.
   • Investigations include actigraphy and polysomnography (PSG) to assess sleep patterns, nocturnal events, and breathing abnormalities.

2. Common Co-existing Medical Problems to Consider:

   • Pain, dental caries, GERD, chronic constipation, seizures, and dystonic spasms.

3. Diagnostic Tools:

   • Overnight PSG for breathing issues.
   • 24-hour video EEG for nocturnal seizures.
   • GI investigations for suspected reflux or gallstones.

Management Strategies:

1. Behavioral and Environmental Approaches:

   • Sleep hygiene: Regular bedtime routines, avoidance of stimulating activities, and creating a calming sleep environment.
   • Avoiding daytime naps, offering deep pressure massages, and using weighted blankets or vibrating mattresses.

2. Pharmacological Interventions:

   • Melatonin: Effective in reducing sleep latency and improving overall sleep quality.
   • Clonidine: Helpful for initiating sleep, though blood pressure monitoring is essential.
   • Benzodiazepines (e.g., clonazepam): May help manage sleep disturbances linked to rigidity or irritability.
   • Antidepressants (e.g., trazodone, quetiapine): Sometimes used to address sleep disorders.

3. Managing Co-existing Issues:

   • Treatment of GERD, seizures, and dystonic spasms is critical.
   • Addressing anxiety and cyclic premenstrual cramps can improve sleep.

Research and Future Directions:

1. Research Gaps:

   • Limited large-scale studies on sleep architecture in RTT.
   • Need for trials comparing RTT sleep patterns with well-characterized cohorts.

2. Focus Areas:

   • Studying genotype-phenotype relationships in sleep disturbances.
   • Developing evidence-based behavioral and pharmacological interventions.

Conclusion:

Effective management of sleep problems in RTT requires a multidisciplinary approach addressing medical, behavioral, and pharmacological needs. Further research is essential to better understand the complex mechanisms underlying sleep dysfunction and to develop safe, targeted interventions.