Rett Syndrome

Excerpt

Rett syndrome (RTT) is a neurodevelopmental disorder in which regression of previously acquired skills follows a period of typical development due to mutations of methylated CpG binding protein 2 (MECP2) gene on the X chromosome. RTT is associated with a complex phenotype and classified into typical, atypical, and variant presentations. Approximately 90% of reported cases of RTT inherit mutations of the MECP2 gene. Some atypical cases of RTT may result from mutations in cyclin-dependent kinase-like 5 (CDKL5). Mutations in MECP2 have been associated with impacting the development of neurons and axodendritic connections. Jellinger and Seitelberger (1986) were the first neuropathologists to identify and describe the pathology behind RTT. They found that the brain in patients of RTT weighed less, and the neurons of the substantia nigra pars compacta contained less melanin in comparison to the age-matched controls. Although RTT primarily affects females, recent studies define males with the phenotype and MECP2 mutations.

RTT presents with a multitude of symptoms but not limited to a deceleration in head growth, abnormal gait, loss of purposeful hand movements often replaced with repetitive stereotypical movement (hand-wringing), rigid movement of hands, loss of language function, breathing abnormalities, and mental retardation. Currently, RTT has no cure; therefore, symptomatic management comprises treatment. Clinical diagnosis, treatment, and genetic counseling of patients with RTT is guided by the revised 2010 third edition of the Diagnostic Standard of RTT and integrated global clinical research reports.