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

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

Stage II, cont. 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

Stage III, cont. 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

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

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