Emma M. M. Burkitt Wright 1,2
Wellcome Trust Clinical Research Training Fellow, Manchester Centre for Genomic Medicine1,2,
lnstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester;2St. Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
Cardio-facio-cutaneous syndrome (CFe} is a multisystem disorder due to germline mutations that cause dysregulation of the Ras-MAPK pathway, and frequently has severe manifestations. Patients demonstrate a wide variety of clinical problems, including neurological features such as learning disability and epilepsy, congenital heart disease and cardiomyopathy, and a wide variety of cutaneous manifestations. Genetic and phenotypic similarities to Noonan syndrome (NS) are present, and as in NS, extensive genetic heterogeneity is demonstrated, and a proportion of patients remain without a molecular diagnosis. These barriers to comprehensive molecular confirmation, combined with the wide variety and variability of clinical manifestations, make it challenging to characterise this disorder fully.
The UK’s national genetic testing service for CFC and Costello syndrome is based in Manchester, and has also diagnosed many patients from elsewhere in the world. Knowledge of this large cohort, now numbering over 200 patients with molecularly proven diagnoses, provides opportunities for better understanding of CFC, and the identification of common and novel features and genotype-phenotype correlations. These findings will allow for better anticipatory management for patients, and can provide critical information when determining future therapeutic goals.