title: Rett syndrome: significant clinical overlap with Angelman syndrome but not with methylation status.
abstract: Rett syndrome and Angelman syndrome are neurodevelopmental disorders characterized by severe intellectual disability, microcephaly, speech disturbance, movement disorders with gait and/or truncal ataxia, and occasionally a similar facial appearance. Both conditions can be difficult to diagnose in girls early in their clinical course and can be difficult to distinguish from each other. Genomic imprinting is a known association in Angelman syndrome and previously has been suggested in Rett syndrome. Our aim was to evaluate the methylation status in a cohort of classical patients with Rett syndrome, using a methylation system for chromosome 15q11-13. Methylation analysis of chromosome 15 has not been previously reported in Rett syndrome. Furthermore, we document the clinical features of 31 girls with classical Rett syndrome and confirm the phenotypic similarities between Rett syndrome and Angelman syndrome. The methylation studies in these girls with Rett syndrome were normal. This excludes an imprinting error of the Angelman syndrome critical region on chromosome 15 (15q11-13) as an association with Rett syndrome, and indicates that methylation studies may be useful in distinguishing Rett syndrome from Angelman syndrome in young patients with an overlapping clinical phenotype. A normal methylation pattern, however, does not exclude the diagnosis of Angelman syndrome and clear distinction between the two syndromes will evolve over time.
authors.affiliation: Department of Paediatrics and Child Health, University of Sydney, New South Wales, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Ellaway
authors.forename: T
authors.initials: T
authors.lastname: Buchholz
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Leonard
authors.forename: J
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D000293:Adolescent; D000328:Adult; D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019175:DNA Methylation; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics*