Snapshot A 3-year-old girl is brought to the pediatrician by her mother. She had been growing well and meeting all her developmental milestones until a few months ago, when she started displaying hand movements that were unusual. On exam, she is active but frequently wrings her hands. Speech and language testing shows that she has regressed to the level expected of a 2-year-old. She is also noted to avoid any eye contact and showed disinterest in playing. She is sent for genetic testing. Introduction Overview Rett syndrome is a degenerative neurological disorder affecting females, caused by sporadic mutation in MECP2 gene on the X chromosome Epidemiology demographics females mutation is fatal in males in utero or soon after birth most common in Swedish, Norwegian, and northern Italian populations Pathogenesis characterized by 4 stages stunted development rapid regression of skills pseudostationary late motor deterioration Genetics inheritance pattern sporadic mutations X chromosome gene MECP2, encoding methyl-CpG binding protein-2 (MeCP2) which is expressed in neural and glial cells Prognosis decreased life expectancy Presentation Symptoms onset of symptoms typically occur between ages 1-4 common symptoms regression of speech and language, motor, and cognitive skills ataxia stunted growth apraxia hand-wringing behavior often the first sign of disease avoidance of eye contact unusual calmness eventually results in cessation of walking gastrointestinal symptoms constipation gastroesophageal reflux difficulty swallowing Physical exam inspection hand-wringing seizure disorder rigidity scoliosis Imaging Radiograph indication evaluate for scoliosis findings scoliosis Barium swallow indication difficulty swallowing findings may have increased tendency for aspiration Studies Genetic testing diagnostic Differential Autism spectrum disorder (ASD) key distinguishing factor patients with ASD typically do not display regression in developed skills Treatment Treatment is aimed at treating symptoms associated with Rett syndrome Lifestyle specialty therapy modalities physical therapy occupational therapy behavioral therapy Medical anti-epileptic medications indications seizure disorder Surgical gastrostomy tube placement indications difficulty swallowing due to neurodegeneration risk of aspiration Complications Aspiration pneumonia Seizure disorder