Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene which encodes the Methyl CpG Binding Protein 2 transcriptional repressor. Rett syndrome affects ~1 in 10,000 females with symptoms including loss of speech and purposeful hand use, microcephaly, seizures, ataxia, and stereotypic hand movements. MECP2 mutations manifest a broader spectrum of clinical phenotypes in female and rare male patients, with features overlapping with other mental retardation disorders. Mutations in the MECP2 coding region can be detected by sequence analysis in up to ~85% of Rett cases (see MECP2 Sequencing Analysis). In addition, large MECP2 gene deletions have been identified in approximately 10% of Rett patients. Our laboratory offers Southern analysis to detect gene rearrangements involving MECP2 (exons 1 through 4) for patients with a documented negative MECP2 sequencing study.