2. RETT’S SYNDROME
Rett syndrome is a neurodevelopmental disorder occurring almost exclusively in
females that affects development after an initial 6-months period of normal
development.
2
3. • Described in 1966 by Andreas Rett.
• X-linked dominant disorder
• Located on q28 on the human X
chromosome.
• Predominantly affects females.
• occurring in 1 : 10 000–15 000 live
female births
• (Burd L, Randall T, Martsolf JT, Kerbeshian J. 1991Rett syndrome symptomatology
of institutionalized adults with mental retardation: comparison of males and
females. Am. J. Ment. Retard. 95, 596–601. )
• Most cases are random, spontaneous
mutations; < 1% of recorded cases are
inherited or passed from one generation
to the next.
3
4. CAUSES
Usually Rett syndrome is caused by a mutation in
the methyl CpG binding protein 2 ( MECP2 ) gene.
The MECP2 gene is involved in the production of a
protein called methyl-cystine binding protein 2 (
MeCP2) which is needed for brain development and
acts as a biochemical switch that can either increase
gene expression or tell other genes when to turn off
and stop producing their own unique proteins.
The MECP2 gene does not function normally in Rett
syndrome
so that structural abnormal forms or inadequate
amounts of the protein are produced and can cause
other genes to have abnormal gene expression
4
5. RESEARCH
Rett syndrome is not always
caused by a MECP2 mutation but
may be caused by partial gene
deletions, mutations in other
genes (eg, CDKL5 and FOXG1
genes) that affect brain
development in atypical Rett
syndrome, mutations in other
parts of the MECP2 gene, and
possibly other genes that have
not yet been identified.
• FOXG1: specific function has
not yet been determined;
however, it may help in brain and
telencephalon (cerebrum)
development
• CDKL5: essential in normal
brain development; acts as a
kinase
5
6. CLINICAL FEATURES
• The course, age of onset, and severity
of symptoms of Rett syndrome vary
from child to child.
• Rett syndrome is characterized by
normal early growth and
development followed by slowing of
developmental milestones, and then
regression of skills with loss of
purposeful hand use with compulsive
hand wringing and washing behavior,
slowed head and brain growth,
seizures, walking difficulty, and
intellectual disability.
• • There are 4 stages used to describe
the symptoms of Rett syndrome.
6
7. • Co-morbidities are common in Rett
syndrome, including gastrointestinal
problems, scoliosis, epilepsy, unusual
breathing patterns, sleep disturbances
and low bone density leading to
increased risk of fractures
• (Downs J, Forbes D, Johnson M, Leonard H. How can clinical ethics guide the
management of comorbidities in the child with Rett syndrome?. Journal of
paediatrics and child health. 2016 Aug 1;52(8):809-13. doi: 10.1111/jpc.13241 )
• Scoliosis is the most prevalent
orthopedic co-morbidity, occurring by
age 15 in approximately 75% of
individuals with Rett syndrome.
• (Downs J, Torodel I, Wong K et al. The natural history of scoliosis in females with
Rett syndrome. Spine 2016;41:856-63. doi: 10.1097/BRS.0000000000001399)
• Altered sensitivity to pain is another
characteristic that individuals with Rett
syndrome may experience.
• (Downs J, Geranton S, Bebbington A et al. Linking MECP2 and pain sensitivity: The example of
Rett syndrome. Am. J. Med. Genet. A 2010;152A:1197-205. doi: 10.1002/ajmg.a.33314)
7
11. 11
• Other disorders with similar symptoms to Rett syndrome must be ruled out before a
diagnosis can be made. Some of these conditions include[15]:
• Autism
• Cerebral palsy
• Other genetic disorders
• Hearing or vision problems
• Degenerative disorders that cause the body or brain to break down
• Brain disorders caused by trauma or infection
• Prenatal brain damage
• (Mayo Clinic. Rett Syndrome Symptoms. http://www.mayoclinic.org/diseases-conditions/rett-
syndrome/basics/symptoms/con-20028086 (accessed 5 May 2017).
DIFFERENTIAL DIAGNOSIS
12. 12
• Management of symptoms Multidisciplinary team support
• There is no cure for Rett syndrome.
• Treatment is optimal with a multidisciplinary approach to address symptoms and
signs.
• A program of occupational therapy, physical therapy, and communication therapy
(with a speech and language therapist) should be provided to address self-help skills
such as feeding and dressing, limited mobility, walking difficulty, and communication
deficits.
• Drugs may be needed to control seizures, for breathing dysfunction or motor
difficulties
• Regular re-evaluation is needed for scoliosis progression and to follow cardiac
abnormalities.
• Nutrition support may be needed to help affected children maintain weight. Special
education programs and social and support services are needed
TREATMENT
13. 13
• Medications can be taken to help with the symptoms like seizures and muscle
stiffness, but can't be taken to cure the disease
• Bromocriptine: test trials with Rett syndrome patients have been used to
improve relaxation and communication skills
• Dextromethorphan: being used to determine if DM will prevent the harmful
over-stimulation of the neurons thereby reducing EEG spike activity and aims
to find out which dose if any will help improve EEG abnormalities, behavior,
cognition, and reduce seizures, as well as improve breathing abnormalities,
motor capabilities, bone density, and GI dysfunction.
• Folate and betaine
• L- carnitine: which may help improve language skills, muscle mass, alertness,
energy and quality of life while decreasing constipation and daytime
sleepiness • L-dopa: for motor rigidity in later stages of the disease
MEDICATIONS
14. 14
• some physiotherapy goals that may be appropriate for a majority of this
population include (but are not limited to):
• Improve mobility and posture and reducing tone (improves feeding
abilities)
• Reducing apraxia through repetitive functional movements/activities
• Increase cardiovascular fitness
• Stimulate hand use (hand splints, fine motor activities)
• Enhance coordination and balance through practice in various situations
and environments
• Improve body awareness through proprioceptive training
• Other therapies including hydrotherapy and hippotherapy
PHYSIOTHERAPY
15. 15
• Kyle Stephanie M. Vashi Neeti and Justice Monica J. 2018Rett syndrome: a neurological disorder with metabolic
component.
• https://www.physio-pedia.com/Rett_Syndrome
• Cash neuro book.
REFERENCES
