Summary Rett Syndrome is a congenital condition caused by an X-linked dominant mutation in the MECP2 gene that affects girls between 6-18 months of age. Patients present with progressive impairment, developmental delays, and spinal abnormalities. Diagnosis is made primarily based on patient development history and clinical observations. Treatment involves a multidisciplinary approach to address developmental delay, cognitive abnormalities, and orthopedic manifestations. Epidemiology Incidence 1 in 10,000 births Demographics male fetuses (only 1 X chromosome) do not survive to term female fetuses (1 mutated gene, 1 normal gene) survive and manifest disease Etiology Pathophysiology affects the grey matter of the brain Genetics inheritance pattern X-linked dominant pattern mutation MECP2 gene mutation this gene encodes the methyl-CpG-binding protein-2, which methylates DNA 95% de novo mutation mutation is on male copy of X chromosome Associated conditions medical conditions development delay seizures 80% of cases behavioral abnormalities screaming and crying loss of speech gastrointestinal constipation orthopaedic spasticity and joint contractures ataxia hypotonia bruxism (grinding of teeth) chorea (abnormal hand movement) scoliosis with C-shaped curve develops at the age of 10 occurs in more than 50% of patients does not respond to bracing instrumentation must include entire scoliotic and kyphotic curve Presentation Symptoms normal development for first 6-18 months of life when symptoms present, they range widely from mild to severe including apraxia loss of purposeful movements in the hands often the first sign of the disease mental slowing (i.e. signs of dementia) abnormal breathing difficulty ambulating seizures Physical exam apraxia abnormal gait scoliosis decreased head circumference usually starts to become evident at 5-6 months poor circulation indicated by cold, blue extremities Imaging Radiographs recommended views AP pelvis findings coxa vara scoliosis films findings C-shaped curve Studies Diagnosis is based primarily on patient development history and clinical observations Genetic testing may identify genetic mutation responsible for disease, though not in all cases Treatment Nonoperative symptom management there is no specific treatment for Rett's syndrome assistance with feeding and hygeine treat seizures physical therapy indicated to avoid hand contracture Operative posterior spinal fusion indications thoracic curve that interferes with sitting and balance C-shaped curve does not respond to bracing technique instrumentation must include entire scoliotic and kyphotic curve Prognosis Half of children unable to walk after the age of ten due to deterioration of motor function development is normal until 6 to 18 months then progressive impairment and development delays occur regression is rapid until the age of three a more stable phase of progression occurs until age of 10