The holiday season, a magical time for so many, can often be very bittersweet for families who love a child afflicted with Rett Syndrome. The holidays can be a painful reminder of the many things our children cannot do: carols they cannot sing, cookies they cannot bake, presents they cannot open, and toys they cannot play with. This season can be especially difficult for the families of newly diagnosed children. It's been 6 years since my daughter's diagnosis. At age 8 she has become a young lady with wisdom and patience beyond her years. Time has softened the raw emotions my family and I experienced during the first difficult year. What time has not softened, however, is the urgency to find treatments and a cure. It is that urgency that spurred the creation of RSRF and that same urgency, shared by our donors and volunteers, that has fueled our growth.

I look back on this year with gratitude for the generous supporters who have enabled scientists to progress in their research. I am looking ahead to 2005 with anticipation and optimism. I am confident it will be a year which will bring us increased understanding of Rett Syndrome. RSRF remains committed to a bold research strategy that will realize our mission of curing this devastating disorder which has robbed our children, and us, of so much.

On behalf of the trustees, staff and volunteers of RSRF I wish you and your families a joyous holiday season.

Sincerely,
Monica Coenraads
Co-Founder and Director of Research, RSRF

This paper discusses the experiences of 8 patients with Rett Syndrome who were prescribed the anti-seizure medication topiramate (topomax). Click here or on the title above to read the abstract.

Dr. Michael Greenberg of Children's Hospital Boston and Harvard Medical Center will be studying the connection between Rett Syndrome and autism. Specifically he will examine a protein called brain-derived neurotrophic factor (BDNF) which is implicated in Rett Syndrome as well as several genes known to regulate BDNF.

Genetics, genomics, bioinformatics and neuroscience join forces
Children's Hospital Boston has begun enrolling patients as part of an ambitious new multidisciplinary study of autism that will attempt to pin down its genetic and biochemical causes. Results could be available in a year or two, and could yield a greater biological understanding of autistic spectrum disorders, better diagnostic and prognostic techniques, and potential medical treatments.

More than 90 percent of autism cases are believed to have a genetic component, and multiple genes are believed to be involved. But although much research has been done and many candidate genes identified, none have been clearly implicated. The Children's study, partially funded by the Nancy Lurie Marks Family Foundation, will bring together researchers in genetics, genomics, bioinformatics, and developmental medicine to try to solve the puzzle.

Autism is a complex behavioral syndrome defined by developmental deficits, particularly communication deficits, impaired social interaction and repetitive behaviors. Affecting about one in 1,000 people, it is now thought of as a spectrum of disorders including autism, Asperger's syndrome and pervasive developmental disorder. There is no specific medical treatment, although behavioral interventions help children on the autistic spectrum live fuller, more functional lives.

The Children's researchers plan to enroll 100 to 150 children age 2 years and older per year, along with their parents and affected siblings. They also will enroll 150 unaffected children to serve as controls. The study has several components:

• The Children's Developmental Medicine Center will first conduct detailed behavioral evaluations of the children and their families, led by Drs. Janice Ware and Leonard Rappaport. Subjects will be assessed for autistic spectrum disorders and carefully classified according to rigorous clinical research criteria. The goal is to develop behavioral profiles that can be correlated with genetic data. Children and their parents will then give saliva samples for DNA analysis and blood samples for RNA gene expression studies.
• Led by Drs. Ingrid Holm and Louis Kunkel, researchers in the Children's Program in Genomics will study the DNA samples, performing association studies and linkage studies to look for genetic differences (polymorphisms) that are shared within families and may accompany clinical manifestations of autistic spectrum disorders.
• The Program in Genomics also will perform microarray ("gene-chip") studies of RNA from white blood cells to examine differences in gene activity, or expression, among autistic children, their parents, and matched control subjects. By looking at 60,000 genes simultaneously and determining which are turned "on" and "off," the researchers will seek patterns or genetic "signatures" that mark the different autistic spectrum disorders and give clues to their biological causes. The investigators hope to show that gene expression in white blood cells is similar enough to that in brain cells to be a useful surrogate measure, avoiding the need to obtain and test brain tissue.
• The Children's Hospital Informatics Program (CHIP), led by Dr. Isaac Kohane, will perform computational analyses to help detect subtle genetic patterns, group patients according to their gene-expression profiles, and apply statistical techniques to determine the reliability of the patterns and linkages found and eliminate false-positive findings. As new data become available, CHIP will factor them in to create the strongest possible predictive models for autistic spectrum disorders.
• The Neurobiology Program of Children's Hospital, led by Dr. Michael Greenberg, will examine the connection between autism, a protein called brain-derived neurotrophic factor (BDNF), and several genes known to regulate BDNF. BDNF regulates many aspects of brain development and function, including formation of synapses. Mutation of one gene that regulates BDNF, called MeCP2, has already been linked to Rett syndrome, which is characterized by mental retardation and autistic behaviors. Further studies of MeCP2 and related genes will explore how they work and how brain-cell activity triggers them. These investigations may uncover other genes and biochemical pathways that underlie autism.
• Children and families enrolled in the Children's study also will be invited to take part in research at MIT's Department of Brain and Cognitive Sciences. Study participants will be tested for their ability to recognize and respond to faces (a critical deficit in autism), the development of specific language skills (also impaired in autism), and gross and fine motor function. Although not a formal part of the study, the data collected by MIT will be fed back into the Children's study and correlated with the genetic data.

Please share your expertise by fillling out the online survey. The purpose of this survey is to ask families living with genetic conditions about their perceptions of their health care providers' knowledge of genetics. The information from this survey will be used to develop genetics education for specific types of health care providers.

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.
PMID: 15605467 [PubMed - in process]