Since 1999, scientists have known that a mutation in a gene called MeCP2 (methyl-CpG-Binding protein 2) can cause Rett syndrome, a neurodevelopmental disorder.
Because not all people with mutations in that gene have Rett, an international consortium of researchers, including physicians from Baylor College of Medicine, created a revised criteria for diagnosing the disease.
"As we work to better understand the disease, new clinical research will be conducted and it is important to have a standard criteria for diagnosis that is applied consistently," said Dr. Jeffrey Neul, assistant professor and assistant medical director of the Blue Bird Circle Rett Center at BCM. "We wanted to create an easy-to-navigate guide for researchers and clinicians."
Rett syndrome is a disease of the nervous system characterized by developmental reversals in areas such as language and motor skills. An infant (usually a girl) seems to develop normally at first. Usually about the age of 1 year, she begins to regress, losing the ability to use her hands and to speak. Other problems involving balance and behavior develop as the disease progresses. While a mutation in the MECP2 gene is often the cause, that is not always the case. Some patients have a mutation in the gene but not the disease. Others may have symptoms of Rett syndrome without the gene mutation.
Regression in motor, language key
"A key part of the criteria we have released is that regression in motor and language functions must be present for a diagnosis of Rett syndrome," said Neul, who is also a faculty member of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. "We can’t make a diagnosis based solely on molecular findings. There is still a significant number of people who have the clinical features but do not have the specific genetic mutation and vice versa, so we cannot equate the two."
Neul adds that a mutation with no clinical signs of regression could be an indication of a different neurological disease that should be treated differently. For example, people with MeCP2 mutations have been diagnosed with autism, symptoms similar to a neurodevelopmental disorder called Angelman syndrome and other intellectual disabilities. These individuals do not appear to regress as one of their symptoms. Additionally, people with Rett-like disease have been found to have mutations in other genes.
In a companion paper that also appears in the Annals of Neurology, Neul and his colleagues used the revised criteria to review information from patients who had been diagnosed with Rett Syndrome previously.
"We didn’t lose cases or have to change a person’s diagnosis, but it made diagnosis a lot easier to assign," he said. "In short, it validated our revisions."
Promoting new therapeutic approaches
The RettSearch consortium is composed of 51 experts in Rett syndrome from 13 different countries. RettSearch’s mission has been to promote the development of new therapeutic approaches for Rett syndrome by collecting information and pursuing research in areas of relevance to clinical trials in RTT.
In the last few years, RettSearch’s goals have expanded to become the authoritative voice of the Rett syndrome community with regard to clinical matters. Neul and Dr. Daniel Glaze, medical director of the Blue Bird Circle Rett Center at BCM and Texas Children's Sleep Center, sit on the executive council for RettSearch.
Funding for the establishment of RettSearch was supported by the National Institutes of Health.
The original article is available at the Wiley online library.
The criteria can also be found on the RettSearch page.