1. Rett Syndrome It’s Not Just for Girl’s Anymore. Craig Dobson, MD CPT, MC, USA NCC Pediatrics Residency Program

2. Clinical Characteristics Developmental regression Progressive microcephaly Stereotyped hand movements Seizures

3. Characteristics Disordered breathing Ataxia Scoliosis Time course progression

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

5. Stage II Age 1-2yr Regression Personality phenotype Difficult to control Screaming fits Occasional self injurious behavior

6. Stage II, cont. Hand movements Wringing Flapping Automatisms Disordered breathing Hyperventilation Apnea Air swallowing

7. 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

8. Stage III, cont. Sleep disturbance Night laughter Early stage III (83%) Night screaming fits later stage III Bruxism Scoliosis

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

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

11. Genetics MECP2 Gene X-Chromosome inactivation Mosaicism

12. Prognosis/Life expectancy Classic Rett Syndrome 7% survive beyond age 40 Unexplained sudden death common Atypical Rett Syndrome Mosaics

13. Clinical Implications Genetic testing Females (incl atypical presentations) Males (mosaics) Genetic couselling Recognition of carrier state Prenatal testing

14. Clinical Implications, cont. New medication options Buspirone for breathing abnormalities Melatonin for sleep disturbances L-carnitine in preserving neurologic function. Targeting learning modalities Music Non-speech communication

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