The Overlapping Spectrum of Rett and Angelman Syndromes: A Clinical Review

Rett and Angelman syndromes comprise part of the spectrum of neurologic disorders associated with autism. Their clinical presentations overlap, with both presenting in later infancy with global developmental delays, severe speech and communication impairments, progressive microcephaly, seizures, autistic behaviors, and characteristic albeit different movement disorders and stereotypic hand movements. Although other features can help differentiate these disorders, significant phenotypic overlap and variation in severity sometimes cloud the underlying diagnosis. Rett syndrome is caused by a mutation in the MECP2 gene located on Xq28, whereas Angelman syndrome results from the loss of UBE3A function on chromosomal region 15q11-q13 related to a variety of molecular genetic mechanisms. Recent advances have uncovered interactions between these and other genes that affect the function and structure of neurons in the brain. The reversal of symptoms of Rett syndrome in a mature mouse model suggests the possibility for treatment of these and perhaps other autism-related disorders in the future.