Presentation
Early neurotypical development. A hallmark of Rett syndrome is neurotypical physical and mental development until 6 to 24 months of age.
Stagnation is the first stage of the syndrome, involving a small but rapid decline in habitual milestones, such motor and language skills.12 Subtle signs, such as microcephaly and hypotonia, can also arise at this time but might be missed.24
Rapid regression follows stagnation. Speech and motor delays and impaired gait and breathing occur;12,25 purposeful hand skills are lost, replaced by repetitive hand-wringing movements that are a hallmark of the syndrome.12,24 Seizures are observed; they become more common during the next stage.12
Plateau. Language advances can be observed, but further deficits are seen in motor skills and hand coordination.12
Late motor deterioration stage. Late physical deficits develop, leading to lifelong impairments. The physical deficits observed are the result of severe muscle weakness, usually resulting in wheelchair dependency.12
Plateau. Patients then reach a second plateau. Regression stops; deficient physical and cognitive states stabilize and are maintained.25
At all stages of Rett syndrome, the following are observed:
- Gastrointestinal problems.
- Sleep disturbances.
- Abnormal cardiorespiratory coupling.
- Greater-than-expected mortality.12
Final regression. The patient is fully dependent for the rest of their lifespan, partially due to seizure activity.26,27
A life-changing diagnosis
A diagnosis of Rett syndrome is life-changing for a patient’s family; access to supportive groups of other patients and their families is extremely beneficial. Two helpful organizations – the Rett Syndrome Research Trust28 and International Rett Syndrome Foundation,29 – offer patient support and community and fund research.
Because X chromosome inactivation is random in Rett syndrome, the individual patient can present with a wide variety of phenotypic combinations – making the patient, and their needs, unique.12 During stages of regression, patients often experience emotional dysregulation and anxiety, which is attributable to their increasing physical difficulties.30 They often exhibit combinations of uncontrolled movements, including repetitive rocking, scratching, and self-injurious behavior.30 For most, regression subsides after the first 5 years of alternating development and regression; after that, their ultimate symptoms persist for life.25
As patients mature, they need to be monitored for proper nutrition and scoliosis.25 As adults, they are at risk of pneumonia, respiratory distress, status epilepticus, osteopenia, and lack of adequate food or water because of impaired ability to feed.25
The lifespan of Rett syndrome patients has increased, thanks to improvements in health care, advances in technology, and early genetic testing, which allows for earlier diagnosis, intervention, and management of symptoms.
Current treatments
When a female patient presents with regression and loss of milestones, sequencing of MECP2 is performed to verify whether Rett syndrome is the cause, by detecting any of the known mutations. Multiplex ligation-dependent probe amplification is also performed to detect major deletions.25
All available treatments for Rett syndrome are symptomatic; intensive early intervention is practiced.31 Multidisciplinary management – medical, psychiatric, and physical – is introduced almost immediately after diagnosis. Following diagnosis, patients are prescribed anti-seizure, sleep, and anxiety medications.31 Electroencephalography can be performed to identify seizure type. Neuromuscular blockage drugs can be prescribed to help with gait and stereotypic hand movements.25
Handguards or splints to the elbows can be prescribed by an occupational therapist to improve hand movement.25 Physical therapy can improve mobility; hydrotherapy and hippotherapy have been successful in helping to maintain mobility and muscle support.32,33 Nutritional management is implemented to control caloric intake and maintain the vitamin D level.31 Some patients experience constipation and urinary retention, putting them at risk of nephrolithiasis.
Once the signs and symptoms of Rett syndrome progress, and milestones regress to a certain point, patients need constant, full-time care for the rest of their lives.34 As symptomatic interventions have greatly improved patient outcomes and it has been shown that about 70% can reach adulthood with a potential lifespan of about 50 years.25
Although there is no cure for Rett syndrome and treatments are symptomatic, ongoing studies – both clinical and preclinical – offer promise that treatments will be developed that work at molecular and genetic levels.