RETT-SYNDROME - SIGNIFICANT CLINICAL OVERLAP WITH ANGELMAN-SYNDROME BUT NOT WITH METHYLATION STATUS

Rett syndrome and Angelman syndrome are neurodevelopmental disorders c haracterized by severe intellectual disability, microcephaly, speech d isturbance, movement disorders with gait and/or truncal ataxia, and oc casionally a similar facial appearance. Both conditions can be difficu lt to diagnose in girls early in their clinical course and can be diff icult to distinguish from each other. Genomic imprinting is a known as sociation in Angelman syndrome and previously has been suggested in Re tt syndrome. Our aim was to evaluate the methylation status in a cohor t of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has no t been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and con firm the phenotypic similarities between Rett syndrome and Angelman sy ndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome cr itical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in dist inguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, howe ver, does not exclude the diagnosis of Angelman syndrome and clear dis tinction between the two syndromes will evolve over time.