Rett syndrome (RTT) is a rare neurodevelopmental condition that primarily affects girls and is usually caused by a mutation in the MECP2 gene. While its hallmark features include loss of purposeful hand use, motor skill regression, and communication challenges, Rett syndrome rarely appears alone.
Because the MECP2 gene influences how many other genes function in the brain and body, people with Rett syndrome often live with a range of comorbid conditions — medical complications that require ongoing attention and care.
Understanding these conditions can help families, caregivers, and clinicians provide better support and early intervention. Below are some of the most common health issues that tend to occur with Rett syndrome.
1. Epilepsy and seizure disorders
Seizures are one of the most frequent complications associated with Rett syndrome. Studies suggest that 60–80% of individuals with RTT experience some form of epilepsy at some point in their lives.
These seizures can vary widely — from generalized tonic-clonic seizures (convulsions involving the entire body) to focal or absence seizures that are harder to detect. In some cases, brief jerks or tremors may even be mistaken for seizures when they are not, making an accurate diagnosis important.
Treatment usually involves anti-seizure medications (AEDs). However, people with Rett syndrome often need careful medication management since some drugs can worsen other symptoms, such as low muscle tone or digestive issues. Regular EEG monitoring helps track seizure activity and guide adjustments over time.
2. Breathing irregularities and apnea
Irregular breathing is another hallmark of Rett syndrome, caused by dysfunction in the autonomic nervous system, which regulates involuntary functions like breathing and heart rate.
Common breathing patterns include:
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Episodes of hyperventilation (rapid breathing)
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Breath-holding spells
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Periods of apnea (temporary cessation of breathing)
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Forceful exhalations or gasping
These issues often happen during wakefulness but can also disrupt sleep. While they may improve with age, some individuals remain at risk for respiratory infections or aspiration pneumonia if their swallowing and breathing coordination is affected.
In severe cases, noninvasive ventilation or airway support may be needed, and families are often trained to monitor breathing patterns closely.
3. Gastrointestinal (GI) problems
Digestive and nutritional challenges are extremely common in Rett syndrome and can significantly affect growth and comfort.
Some of the most frequent GI complications include:
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Constipation, often due to reduced gut motility
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Gastroesophageal reflux disease (GERD), leading to discomfort or vomiting
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Bloating and gas caused by swallowing air during hyperventilation
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Difficulty chewing or swallowing (dysphagia), which can increase the risk of aspiration
Because of these challenges, many individuals struggle to maintain a healthy weight or get adequate nutrients. In such cases, gastrostomy tubes (G-tubes) may be used to provide reliable nutrition while minimizing choking risk.
Dietary adjustments, fiber supplements, and feeding strategies from occupational or speech therapists can all help improve quality of life and prevent complications.
4. Scoliosis and orthopedic issues
Skeletal changes are another well-known part of Rett syndrome’s progression. Scoliosis, a sideways curvature of the spine, affects more than half of all individuals with RTT, often beginning around age 8 to 11.
Muscle tone changes (from low tone in early years to rigidity later) and limited mobility contribute to spinal curvature, joint contractures, and hip dislocation.
Monitoring spinal alignment is essential, as severe scoliosis can interfere with lung capacity and sitting balance. Orthopedic braces, physical therapy, and in some cases spinal fusion surgery may be recommended.
Additionally, low bone density (osteopenia or osteoporosis) is common and leads to a higher risk of fractures. Adequate vitamin D, calcium intake, and weight-bearing exercises can help strengthen bone health.
5. Sleep disturbances
Sleep problems are extremely common in Rett syndrome, affecting both the individual and their caregivers.
Common sleep-related issues include:
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Difficulty falling asleep or staying asleep
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Frequent nighttime awakenings
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Restless or irregular sleep patterns
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Sleep-disordered breathing or sleep apnea
These disturbances may be linked to abnormal melatonin regulation, autonomic dysfunction, and discomfort caused by other symptoms like reflux or pain.
Maintaining a consistent bedtime routine, adjusting medications that may interfere with sleep, and monitoring for breathing issues can all make nights more manageable.
6. Cardiac and autonomic dysregulation
Rett syndrome affects the body’s autonomic control systems, which means heart function can also be impacted.
A significant concern is QT interval prolongation — an irregularity in the heart’s electrical rhythm that can increase the risk of serious arrhythmias. For this reason, regular EKG screenings are recommended for anyone with RTT.
Other signs of autonomic dysfunction may include:
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Cool or bluish hands and feet
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Changes in sweating
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Temperature regulation issues
These symptoms can vary day to day and are typically managed through monitoring and medication adjustments guided by cardiologists familiar with Rett syndrome.
7. Pain and sensory dysregulation
Many individuals with Rett syndrome experience pain that may go unrecognized because of limited communication abilities. Common sources of discomfort include:
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Gastrointestinal pain (from constipation or reflux)
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Muscle stiffness or joint pain
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Fractures or spinal issues
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Dental or jaw pain due to teeth grinding (bruxism)
Families and clinicians often rely on nonverbal cues — facial grimacing, irritability, or body posturing — to identify discomfort. Specialized pain scales for nonverbal individuals are increasingly being used in Rett care settings.
8. Growth and endocrine issues
Growth delays are common in Rett syndrome and can appear early in childhood. Many individuals are smaller or lighter than their peers, even when nutrition is adequate.
Some also experience pubertal delay or other hormonal irregularities. Regular monitoring of growth patterns and endocrine function helps identify issues early and guide interventions.
9. Anxiety, agitation, and mood Changes
Although Rett syndrome is primarily neurological, behavioral and emotional symptoms are part of the clinical picture.
Episodes of anxiety, agitation, or screaming may appear suddenly and without an obvious trigger. These can be caused by physical discomfort, autonomic changes, or neurological overstimulation.
Supportive care may include environmental adjustments, sensory tools, and, in some cases, selective serotonin reuptake inhibitors (SSRIs) or other medications to manage severe anxiety.
10. Immune and respiratory vulnerability
Frequent respiratory infections are common in Rett syndrome, especially among individuals with poor swallowing coordination or scoliosis that restricts chest movement.
Preventive care — such as vaccinations, airway clearance exercises, and prompt treatment of infections — helps protect respiratory health.
Monitoring for aspiration pneumonia (food or liquid entering the lungs) is crucial, as it’s one of the leading causes of hospitalization in people with RTT.
Why So Many Conditions Occur Together
All of these complications stem from the broad role of the MECP2 gene, which influences brain signaling, autonomic control, and even how other organs develop and function.
Because MECP2 affects so many biological systems, its disruption leads to a cascade of symptoms — not just motor and cognitive changes, but also systemic effects on breathing, digestion, bone, and heart function.
Living With Rett Syndrome: A Whole-Body Approach
Managing Rett syndrome requires a multidisciplinary care team that may include neurologists, gastroenterologists, pulmonologists, orthopedists, cardiologists, dietitians, and therapists.
The Rett Syndrome Comprehensive Care Guidelines recommend proactive monitoring of:
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Seizures and EEG activity
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Heart rhythm and QT interval
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Bone density and scoliosis progression
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Growth and nutrition
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Sleep and breathing patterns
Because Rett syndrome affects nearly every system of the body, early detection and coordinated care can prevent complications and improve long-term quality of life.