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Cardiofaciocutaneous Syndrome and Noonan Syndrome Scientific Meeting Nov. 17-19, 2006 Potomac, Maryland Meeting report by J. Jasper (1-16-07) Genes are composed of DNA and the genes code for the different proteins in our bodies. Sometimes, mutations in the DNA occur in an embryo and this causes corresponding mutations in the proteins; such mutations in the proteins can lead to disease. We now know that Noonan Syndrome can be caused by mutations in the protein Shp-2 (encoded by the PTPN11 gene), KRAS, and what was reported at this meeting for the first time, the protein SOS1. Mutations in these three genes (and their corresponding proteins) account for about 50%, 2-4% and about 10% of Noonan Syndrome cases, respectively. So we understand the molecular basis for about 65% of the Noonan Syndrome cases; the other 35% we are still searching to understand. Let me re-state this point: Noonan syndrome (NS) can be caused by mutations in the Shp-2 protein (about 50% of the time), the KRAS protein (2-4% of the time) or the SOS1 protein (about 10% of the cases). The other 35% of Noonan Syndrome patients likely have a mutation in a gene/protein that we have not yet ‘discovered’. The severity of NS symptoms depends on the particular mutation as well as other genetic factors that influence the protein of interest. Each of the proteins Shp-2, KRAS and SOS1 are involved in particular cellular signaling pathways necessary for development and growth. CFC syndrome and Costello Syndrome (CS) patients also have mutations in this pathway (BRAF and MEK genes for CFC, or the HRAS gene for CS). The meeting had discussions about these recent discoveries and how we can now better understand the diseases. Many discussions involved the molecular and clinical description of CFC syndrome, CS and NS. Because a firm clinical diagnosis of these conditions can be difficult, molecular definition of the conditions would be useful. However, it is not that simple and the symptoms of the conditions often overlap. We still have a lot to learn in this area and it will be important to establish registries for the data and guidelines for diagnoses. There were some nice discussions around various symptoms that patients deal with such as heart disease (e.g. hypertropic cardiomyopathy and pulmonary stenosis), feeding difficulties and gastrointestinal issues, lymphedema, leg pain, slow growth or failure to respond to growth hormone therapy, night sweats, malignant hyperthermia, myelodysplastic syndrome and leukemia, learning disorders, depression, etc. The details of these discussions can be found in the latest NSSG newsletter [WANDA, LINK HERE?]. There were also some complicated scientific discussions describing fruit fly and mouse models of NS (yes, fruit flies have these genes too!). Dr. Amy Roberts and Dr. Bruce Gelb, along with help from many others, did a great job in establishing a meeting to bring together researchers and clinicians to better understand and treat patients with CFC syndrome, CS and NS. Most in the audience agreed that another meeting focusing on these cellular signaling pathways would be helpful (probably in 2009). Hopefully, as we all gain a better understanding, therapies might be devised to best help patients.
A more detailed (updated) report is available
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