The Rett Syndrome, MECP2 Duplication Disorder, and Rett-related Disorders RDCRN consortium is an extension of the previous activities of the Rett syndrome Natural History Study (NHS). During the previous NHS, MECP2 Duplication disorder and Rett syndrome-related disorders became prominent considerations and other mutations, CDKL5 and FOXG1, resulted in neurodevelopmental disabilities which overlapped with Rett syndrome.  As a result this newly developed consortium will cover the NHS of these disorders to provide additional phenotype-genotype correlations and to lead to advanced studies addressing potential biomarkers, neurophysiologic and neuroimaging correlates, and outcome markers for emerging clinical trials.  Clinical trials already in place have demonstrated the critical need for robust outcome measures among these a neurobehavioral outcome metric that will be the target of our initial pilot study.  A second study will examine the metabolic profiles of individuals with these specific disorders in particular guided by advance proteomics.  In addition, training of young investigators in clinical research aspects will be pursued actively during this funding period. 

Mission Statement

To conduct longitudinal clinical assessment of the natural history of Rett syndrome, MECP2 Duplication disorder, and Rett-related disorders including individuals with mutations in CDKL5, FOXG1, and MECP2 not meeting criteria for Rett syndrome; to develop phenotype-genotype correlations in each disorder; and to set the stage for conduct of translational studies and emerging clinical trials leading to disease modification.


A) Continue to explore the phenotype-genotype relations in Rett syndrome and explore these relationships in MECP2 Duplication disorder, and the Rett-related disorders including CDKL5, FOXG1, and individuals with mutations in MECP2 but not fulfilling the consensus criteria for Rett syndrome.

B) In Rett syndrome, this will include a more in depth look at X chromosome inactivation and in other related gene products such as BDNF.

C) Develop through complex neurophysiologic and neuroimaging a better understanding these markers of biologic involvement.

D) Develop a set of biomarkers through metabolic and proteomic studies in blood.

E) Develop a set of behavioral outcome measures that will provide important endpoints for planned clinical trials.