Autism and Developmental Disorders Colloquium Series

“Rett Syndrome: Clinical insights from a neurodevelopmental disorder with a known genetic cause”

Omar Khwaja , MD , Ph.D.
Director, Rett Syndrome Program

Department of Neurology, Children's Hospital Boston

6:00 p.m., Wednesday, October 17, 2007
MIT Building 46-3002 (auditorium), followed by a reception

Building Address: 43 Vassar Street, Cambridge, MA 02139

Hosted by Mriganka Sur, Ph.D., and the Brain Development and Disorders Project at MIT

Supported by the Simons Foundation, the Anne and Paul Marcus Family Foundation, and the Autism Treatment Network

Colloquia sponsored by the Autism Consortium

Please RSVP to lmavros@mit.edu

Rett syndrome (RTT) is a severe pervasive neurodevelopmental disorder with symptoms beginning in early childhood. Primarily associated with mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, RTT is characterized by both developmental regression and profound motor and language impairment. RTT affects 1 in 10,000 female births and is the leading known genetic cause of autism spectrum behaviors in girls. Diagnostic criteria include deceleration of head growth, loss of hand skills, stereotypies, loss of acquired speech, apparent cognitive decline and motor impairment. RTT has significant overlap with other forms of autism and neurogenetic disorders associated with normal early infant development followed by psychomotor regression. Features specific to RTT include a characteristic motor syndrome, prominent respiratory, autonomic and emotional-behavioral disturbances and preserved eye gaze. Electrophysiological abnormalities including epilepsy and sleep disorders are frequent, as are disorders of somatic growth, nutrition and gastrointestinal motility. Symptoms tend to be dynamic rather than progressive during early childhood and there is significant fluctuation in adaptive function. The clinical features and longitudinal course of RTT suggest specific neuro-anatomic regions and neuronal networks are spatially and temporally vulnerable to impaired synaptic maintenance or modulation. Pharmacotherapy primarily targets neurological symptoms with combinations of antiepileptic and psychotropic medications, together with anti-spasticity agents. Therapy is frequently empiric but there is emerging evidence for more rationale drug selection. Robust outcome measures suitable for clinical trials are urgently needed to assess currently available pharmacotherapy and to translate novel agents identified during preclinical studies.