Sara-Jane White N.D.
The lack of evidence based research for the efficacy of physical and/or occupational therapy in
Rett syndrome (RTT) limits the clinical practitioner and therapist in their ability to recommend
treatment to RTT families. RTT presents with an array of therapy challenges due to the high
variability in RTT phenotypes and the systemic nature of its neuropathology. Considerations
need to be made for: coordination and balance issues, bone pathologies, scoliosis, behaviour
issues, sensory integration pathologies, loss of communication, loss of fine and gross motor, loss
of transition and posture, foot deformities and depth perception pathologies resulting in spatial
An educated and intense therapy may be helpful in particular severity levels of RTT. The
purpose of this article is to present therapy findings in similar disease pathologies to RTT in the
hope these already published findings could be transferred to RTT therapy and treatment. The
article also presents the author’s viewpoint with regard to physical therapies and the implications
in RTT specific pathologies. Major RTT centers need to organize evidence-based research to
categorize RTT symptoms with a grading system for severity and determine which symptoms
and at what severity intense physical therapy advances the skills of RTT patients and allows for
increased quality of life.
Key Words: Rett Syndrome, physical therapy, strength training.
Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by the loss of acquired
motor and communication skills, autistic features and unusual stereotyped movements that
primarily involve the hands (1). RTT is typically caused by mutations on the X-linked gene
encoding methyl-CpG binding protein 2 (MeCP2) (2). Depending on the severity of the mutation
and due to X-inactivation skewing there can be a variety of phenotypes and the loss of skills can
occur anywhere between 3mths of age to 3 years of age (2,3,4). RTT is considered a postnatal
disorder but with an in depth clinical intake most cases report lower than normal fetal movement
and abnormal movement before the period of regression indicating abnormal gross and fine
motor development may begin in utero (5).
Presently RTT is calculated to affect one in every 10,000 females and despite the high incidence
and the unique features it still goes undiagnosed or misdiagnosed (6,7). Most RTT females meet
the expected motor and cognitive milestones in the early stages of development but after this
apparent normal development they enter a stage of regression during which communication skills
are lost and they develop ataxia, apraxia, incessant hand stereotypies and eventually lose
purposeful fine motor skills. Other features develop including swallowing pathologies, gut
motility pathologies, social impairment, seizures, breathing dysfunction, deceleration of head
growth and bone pathologies with scoliosis. After the regressive period most patients stabilize
and are considered unable to learn new skills. The majority of patients survive into adulthood but
may also develop additional neurological abnormalities such as Parkinsonian features of
increasing ataxia, rigidity and increased postural instability (2, 4,8,9,10).
There is no cure for RTT but interventions may improve the quality of life and minimize the
severity of symptoms. Since the discovery of the gene that causes RTT in 1999 (11) there has
been a wave of interest within the research community to understand the biogenetic pathways of
the disease. Unfortunately, there has not been the same interest within the medical community to
investigate therapies leaving parents with no thorough evidence based research or randomized
control trials to identify appropriate physical/cognitive techniques to advance the skills of their
Rett children. The following views, therefore, are only a viewpoint and not based in research on
Rett patients and solely written to provide recommendations for therapists and practitioners.
A multidisciplinary team is required when treating a RTT patient as there are many facets to the
syndrome. When designing a therapy regime the goals are to help the RTT patient overcome the
disease limitations of coordination and balance pathologies, apraxia, ataxia, bone density
pathologies, underweight/overweight metabolic pathologies, hypotonia/hypertonia, and muscle
Indications therapy must be approached with caution:
those with mobility have small gait, in theory due to hypotonia and muscle weakness (12)
there are reports of increased DTR (13)
At submaximal and maximal workloads there is no currently quantified data re: heart
rate, oxygen consumption, minute ventilation or muscle tone therefore no assessment can
be made regarding the safety of aerobic conditioning
The respiratory distress in most Rett patients may lead to abnormal respiratory muscles
and lower maximal oxygen consumption
For those with ambulation a treadmill stress test would be required to analyze
cardiovascular ability and improvement with therapy but muscular fatigue may occur
before the cardiovascular system is maximally stressed due to a lack of oxygen from
abnormal respiratory muscles
Abnormal QT wave irregularities are reported (2)
From my clinical experience RTT patients suffer from depth perception pathologies
causing a fear of movement and postural changes
Osteopenia and osteoporosis have been reported as early as 2 y.o. resulting in a weak
bone matrix leaving RTT patients at a high risk for fractures (9,10)
Foot deformities (2)
There are a wide range of Rett phenotypes and the abilities and behaviour vary greatly for each
patient. During the Four Stages of Rett (developmental stagnation, regression, stability with the
possibility of seizures and other symptoms developing, late motor deterioration) (2,8), therapy
must be adjusted and re-evaluated for each stage per patient. An individualized therapy must be
created and rarely do rules exist that will apply to all Rett girls. The most important aspect of a
paediatric rehabilitation program especially when the child does not have expressive speech is to
recognize the child’s cues and tolerance levels, there needs to be a balance between physically
and cognitively challenging the patient yet not creating a stressful environment. Minimizing
stress, especially during the regression period in RTT is critical (14). For any therapy in RTT
there are possibilities but there are also limitations as mentioned in the previous section.
Repetitive hand movements are the hallmark of RTT (1,2,15). From anecdotal observations of
parents ‘when the stereotypic hand movements are inhibited, many girls are more social and
interact more with the environment while they decrease hand to mouth movements and hand
wringing behaviour’ (14). Clinically, it has been observed that Rett girls are more interactive
with their surroundings and peers and have more functional use of their hands when they are
restricted from the stereotypic movements. Decreasing repetitive purposeless hand movements is
also helpful in decreasing agitation and self-injurious behaviour. (2, 16)
The ability of hand skills will vary depending on the age of regression i.e. if the pincer grasp was
developed before regression the skill of hand coordination may be higher during the stability
period of development. The therapist must identify when the child has stereotypic hand
movements: constantly, when angry, in pain, sad, over-stimulated or happy/excited and then use
their clinical judgement as whether to fully restrict hand stereotypies.
Typical Rett hand movements are (14):
hands held apart but with finger/thumb rolling
The standard so far to prevent the repetitive hand movements of RTT is hand splinting. Three
forms of splints are typically used, elbow splints which extend the length of the forearm to just
above the elbow, full hand splints which extend from above the finger tips to just below the wrist
leaving the thumb free and half hand splints which extend below the wrist to the first finger
joints (14). Full hand and half hand splints may interfere with fine motor training and therapy.
In my clinical opinion I recommend wrist weights as an alternative form to restricting the hand
stereotypies. Wrist weights do not impede occupational therapy exercises and would bring a
strength-training feature to the treatment/therapy.
The principles of strength training applies to the pathogenesis of RTT therapy but have not been
used in practice. Strength training is not weight lifting and the emphasis is not on the amount of
weight used but on developing controlled movements. A lightweight around the wrists decreases
mild ataxia because the muscles are working against resistance. Light wrist weights will also
leave the hands completely free to develop fine motor skills without danger of straining muscles,
tendons or growth plates which is particularly important due to the bone pathologies previously
stated. In essence, the principles of the weighted vest can be transferred to the hands when
specifically isolating fine motor therapy. The weighted vest was designed to reduce purposeless
behaviours, inattention and hyperactivity in children with sensory integration dysfunction. When
applied to the wrists during fine motor training for a Rett patient the same affect would be
observed and there is the additional benefit of strength training.
increases muscle strength and endurance
protects muscles and joints from injury
develops stronger bones
improves heart and lung function
healthy body composition
lowers blood cholesterol levels
improves hormone metabolism
improves balance and co-ordination
RTT is the second major cause of MR in girls after Down Syndrome (DS) (17). DS was the first
genetic disorder attributed to a chromosomal abnormality (12). DS presents with similar
orthopaedic impairment: including hypotonia and muscle weakness, cardiovascular,
neurological, cognitive, hormonal, and visual perceptual impairments with obesity being a
common problem (12). DS also shares the common feature of alterations in dendritic spines and
synapses as the primary neuropathology as in RTT (4).
Aerobic training studies on DS patients using ACSM guidelines indicated improved endurance
but no change in cardiovascular function such as resting HR or submaximal HR, VO2 and VE.
Subjects who completed 30 minutes of aerobic activity at 65% to 75% VO2 maximum three
times per week increased their aerobic endurance as seen by walking longer on the treadmill or
rowing longer on an ergometer indicating increased aerobic performance. The study found a high
correlation of strength to VO2 during treadmill stress testing suggesting that a combined strength
training and aerobic conditioning program may be more effective for enhancing cardiovascular
function in DS than aerobic training alone (12).
A single case study on a 10.5 y.o. girl with DS was conducted using aerobic conditioning and
strength training for 30-60 minutes daily at 70% to 80% intensity for six days per week. The
authors of this study emphasized that ‘individualized exercises along with parental support’
allowed the study to be a success. The authors are referring to recognizing motivators for the
subject and program adherence. Ultimately the parents were pleased with the success but could
not maintain the intensity of the program after the study, regardless, when the parents adjusted
the exercise program to their coping ability several months later they reported continued success
with endurance, enhanced community mobility and weight management (12).
The authors concluded in this single case study that a combined aerobic conditioning and
strength training of moderate to high intensity, 30 to 60 minutes per day for 5 to 6 days per week
resulted in changes in cardiovascular function not reported in other studies employing aerobic
conditioning alone (12).
In a recent evidence based literature review of physical therapy in Parkinson’s disease; which
also shares the clinical features of RTT such as ataxia, gait pathologies, postural changing and
rigidity and fine motor pathologies, six specific core areas were identified for physical therapy
for Parkinsonian features. (1) Transfers (from one position to another), (2) postures, (3) reaching
and grasping, (4) balance and falls (including fear of falls), (5) gait, (6) physical capacity and (in)
activity. The authors used international criteria (18,19,20) for guideline development and
developed evidence-based practice recommendations. In the review article four practice
recommendations were based in evidence from two or more controlled trials therefore reaching a
Level 2 classification in EBRO classification of study results and recommendations suggesting
an adequate level of evidence they improved some aspect of the six core areas. The four practice
recommendations are: (1) application of cueing strategies to improve gait, (2) application of
cognitive movement strategies to improve transfers, (3) specific exercises to improve balance,
(4) training of joint mobility and muscle power to improve physical capacity (18).
Visual, auditory, tactile and cognitive cues are ‘encoded’ during normal gait development. In
theory gait may be improved with learned visual or auditory cues. Cues are stimuli from the
environment or generated by the patient, which the patient uses consciously or not to facilitate
automatic or repetitive movements. Auditory cues use rhythmic music, a metronome or counting;
visual cues use techniques such as stepping over stripes on the floor. ‘It is not clear how cues
improve movement but the authors theorized they provide an external rhythm that can
compensate for the improperly supplied internal rhythm of the basal ganglia, correct the motor
set deficiency, or in the case of visual cues generate optical flow that activates a cerebellar
visual-motor pathway’ (18)
Cognitive motor strategies take complex automated movements and transform them into a series
of sub-movements that have to be executed in a fixed pattern. The activity can then be performed
consciously. ‘The fundamental problem of the disturbed internal control can be bypassed. The
newly learned movement sequence does not become automated but performance remains under
conscious control and can be improved with cues’ (18). The literature review found evidence
transfers were improved using cognitive movement strategies.
The authors found it probable balance training using visual and vestibular feedback combined
with lower limb strength training was effective in improving balance in patients with PD and is
more effective than balance exercises alone. They also identified the efficacy of an exercise
program aimed at improving range of motion combined with activity related exercises such as
gait and balance improves activities of daily life functioning. And, a strength-training program
increases muscle power (18).
Implications for RTT:
For a certain severity level early intervention with treadmill therapy using wrist and ankle
weights may aid in transfer coordination issues, balance and gait pathologies by
improving gross and fine motor function, maintain hormonal balance and improve
endurance and increase muscle strength and aid cardiovascular function and ultimately
lead to increased quality of life.
Increased tone in the Achilles tendon is the earliest sign of the onset of muscular rigidity.
Bilateral foot/ankle orthoses need to be used to prevent foot deformity, maintain foot
alignment and keep the heel cord strengthened.
Small frequent meals with high carbohydrate content not only decreases gut motility
pathologies of reflux but maintains growth and weight gain in the underweight RTT girl
(16, 21) and allows for an even release of insulin to maintain peak fitness abilities
throughout the day.
Learned cueing strategies; when used with treadmill therapy, with repeated exposure and
practice may overcome the fear of movement, improve postural changes, gait, transfers
and increase physical capacity and muscle strength.
Applying cognitive movement strategies to improve transfers may not be considered
possible in RTT by the current medical establishment, however, if a complex movement
is broken down and repeated a ‘motor memory’ may develop. Apraxia can be reduced by
repetitive functional experiences and allow for a higher functioning RTT patient.
Scoliosis is present in approximately 65% of RTT patients (2). Regressing the
progression of scoliosis can be achieved through physical therapy. The below list is taken
from Meir Lotan’s Physical therapy Intervention for Individuals with Rett Syndrome (22).
o Intensive physical and hydrotherapy treatments were reported to yield the
maximal benefits according to the results of a questionnaire completed by 107
parents and caregivers in the U.S. (Rossin 97)
o Aggressive treatment starting as soon as the first spinal asymmetry is noticed was
suggested by McClure, Battaglia and McClure (98), who found a close correlation
between the primary asymmetry of the back and the later developing scoliosis,
according to 262 responses to a questionnaire completed by IRSA families.
o Intensive walking, or standing if the individual is non-mobile, was suggested by
Lyn Weekes (97), for at least half an hour a day. This element of the program is
also supported by the relationship found between walking and reduced percentage
of spinal operations (Rossin 97).
Detailed subgroups of RTT females need to be developed to properly create and adapt therapy.
RTT centers should develop quick reference referral cards for distribution to large paediatric care
facilities featuring in great detail RTT symptoms. RTT centers need to develop a coding system
for grading the symptom severity. Studies need to be completed at the major Rett centers to
determine at what level of severity of symptoms is therapy beneficial and at what intensity can
therapy be maintained. Only then will parents have the proper information to allow them to
maintain a home based physical therapy training program to improve the quality of life of their
children and by extension the quality of life of the caregiver and patient family.
Making individualized wrist and ankle weights can be accomplished by purchasing the standard
wrist weights and then removing the small weights and sewing them into soft cloth. Start with
one small weight and then gradually increase to the child’s ability. Fasten weights with Velcro.
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