Rett Syndrome

by Mary, Sherry & Kate

 Characteristic
s

 progressive neurodevelopmental disorder

 Autism spectrum
 affects females almost exclusively, leading cause of severe mental retardation

Normal early growth and development for first 6-18 months of life
Growth stagnation
Symptoms appear in stages
Severe regression in language & motor skills
Seizures, affect ~80% (2-10 years +) (Vignoli et al., 2010)

Incidence in Australia 1/9,000

(Urbanowicz, Leonard, Girdler, Ciccone, & Downs, 2014)

Image source: retrieved 2 August, 2015

rsrt.org/rett-and-mecp2-disorders/thereishope/
 Onset &
Progression

(Chahrour & Zoghbi, 2007)

 Rett Syndrome –a new class of disease

Spontaneous genetic mutation of X-linked gene MECP2 discovered in 1999 (Amir et al., 1999)

MECP2 gene makes the protein MeCP2

 gene regulator - “off switch”
loss of function = overexpression
 gene activator -“on switch” in hypothalamus (Chahrour et al., 2008)
loss of function = poor expression
 damage to:

nervous system maturation (Amir et al., 1999)

brain centres that control movement & emotion

Source:retrieved 2 August 2015 https://en.wikipedia.org/wiki/MECP2

 Classic
Rett Syndrome

MECP2-related
Variant severe neonatal
Rett Syndrome encephalopathy
MECP2-related Males most common phenotype: death

disorders before age two years (Christodoulou &

Ho, 2012)

MECP2
duplication PPM-X Syndrome
syndrome

Course & severity typically depends on location, type & severity of MECP2 mutation
(Neul et al., 2008)

Over 99% cases not inherited, no family history, simplex cases (Christodoulou & Ho, 2012)

(Rett Syndrome, 2015)

 Diagnosis &
Treatment

 Observation of symptoms and behaviour (Chahrour & Zoghbi, 2007)

 Genetic testing can help confirm diagnosis in 80% girls
 Brain activity tests (EEG)

No cure

 Supportive measures, e.g. occupational therapy (e.g. orthopedic braces), medication,

hydrotherapy

Source: retrieved 3 August 2015 from http://www.thechildrenstrust.org.uk/image-

cache/image-1542-orig.jpg
 The search for a
cure

Partial reversal of Rett syndrome-like symptoms in MeCP2 deficient mice (using peptide
treatment)
(Tropea et al., 2008)

Human patients with milder phenotypes despite severe MeCP2 mutations – suggests other
protein(s) may lessen severity of disease
(Chahrour & Zoghbi, 2007)

Source:retrieved 1 August 2015 from

cnbc.pt/images/UebeImg/Noticias/Img_111_574.jpg
 References
Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999). Rett syndrome is
caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature genetics, 23(2), 185-188.
doi:10.1038/13810
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J., & Zoghbi, H. Y. (2008). MeCP2, a key contributor
to neurological disease, activates and represses transcription. Science, 320(5880), 1224-1229.
doi:10.1126/science.1153252
Chahrour, M., & Zoghbi, H. Y. (2007). The story of Rett syndrome: from clinic to neurobiology. Neuron, 56(3), 422-
437. doi:10.1016/j.neuron.2007.10.001
Christodoulou J., & Ho, G. (2012). MECP2-Related Disorders. In: Pagon R. A., Adam M. P., Ardinger H. H., et al.,
(Eds). GeneReviews. Retrieved August 1, 2015, from http://www.ncbi.nlm.nih.gov/books/NBK1497/
Neul, J. L., Fang, P., Barrish, J., Lane, J., Caeg, E., Smith, E. O., … Glaze, D. G. (2008). Specific Mutations in Methyl-
CpG-Binding Protein 2 Confer Different Severity in Rett Syndrome. Neurology, 70(16), 1313–1321.
doi:10.1212/01.wnl.0000291011.54508.a
Rett Syndrome (2015). Retrieved August 1, 2015, from http://rarediseases.org/rare-diseases/rett-syndrome
Rett Syndrome Fact sheet (n.d.). Retrieved August 1, 2015, from
http://www.ninds.nih.gov/disorders/rett/detail_rett.htm
Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., ... & Sur, M. (2009). Partial reversal of
Rett Syndrome-like symptoms in MeCP2 mutant mice. Proceedings of the National Academy of Sciences, 106(6),
2029-2034.
Urbanowicz, A., Leonard, H., Girdler, S., Ciccone, N., & Downs, J. (2014). Parental perspectives on the
communication abilities of their daughters with Rett syndrome. Developmental neurorehabilitation, (0), 1-9.
doi:10.3109/17518423.2013.879940
Vignoli, A., Fabio, R. A., La Briola, F., Giannatiempo, S., Antonietti, A., Maggiolini, S., & Canevini, M. P. (2010).
Correlations between neurophysiological, behavioral, and cognitive function in Rett syndrome. Epilepsy & Behavior,
17(4), 489-496. doi:10.1016/j.yebeh.2010.01.024