Rett Syndrome (It’s Not Just for Girl’s Anymore)

Rett Syndrome


Clinical Characteristics

Developmental regression
Progressive microcephaly
Stereotyped hand movements
Seizures

Characteristics

Disordered breathing
Ataxia
Scoliosis
Time course progression

Stage I
Age 6-18 months
Minor delays
Postural reflexes delayed
‘Bottom shuffling’ common
Often normal

Stage II
Age 1-2yr
Regression
Personality phenotype
Difficult to control
Screaming fits
Occasional self injurious behavior
Hand movements
Wringing
Flapping
Automatisms
Disordered breathing
Hyperventilation
Apnea
Air swallowing

Stage III
Usually begins age 3-4
Regaining and improving communication
Improved behavior
Stable to slowly declining motor function
Seizures
Generalized or partial
Late stage II to early III
Sleep disturbance
Night laughter Early stage III (83%)
Night screaming fits later stage III
Bruxism
Scoliosis

Stage IV
Adult life
Progressive lower motor deterioration
Progressive severe neurogenic scoliosis
Preserved communication
Improved control of seizures
Improved behavioral phenotype

Epidemiology
1:10,000-15,000 females
Rare but present in males
Unknown atypical prevalence

Genetics
MECP2 Gene
X-Chromosome inactivation
Mosaicism



Prognosis/Life expectancy

Classic Rett Syndrome
7% survive beyond age 40
Unexplained sudden death common

Atypical Rett Syndrome
Mosaics

Clinical Implications

Genetic testing
Females (incl atypical presentations)
Males (mosaics)

Genetic couselling
Recognition of carrier state
Prenatal testing

New medication options
Buspirone for breathing abnormalities
Melatonin for sleep disturbances
L-carnitine in preserving neurologic function.

Targeting learning modalities
Music
Non-speech communication

Future
Expanded genetic testing
Recognition of more atypical presentations
Mouse model testing of therapeutics
Further understanding of gene’s regulatory role