RASopathies is the term for a clinically and genetically heterogeneous group of disorders that are caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated-protein kinase pathway. The Ras/MAP kinase signaling pathway plays an essential role in the regulation of the cell cycle, differentiation, growth and apoptosis; processes which are crucial for normal development. Dysregulation of this pathway has a profound impact on development. Most mutations causing the syndrome are activating changes which increase signal transduction within this pathway. Several organ systems, such as the cardiovascular system, skeleton, muscles, gastrointestinal tract, CNS, eyes, are affected. The syndromes overlap significantly in their signs and symptoms, which may complicate establishing a clear diagnosis and targeted diagnostic procedures. Moreover, several of these disorders may be caused by mutations in various genes of the Ras/MAPK pathway. Early identification of individuals at risk can help establish the right clinical management plan.
We offer comprehensive and syndrome-specific panels testing for RASopathies. The test can offer a molecular genetic diagnosis of a RASopathies that is observed or predicted in you or a family member.
IMPORTANCE OF GETTING TESTED
If you or a family member has a risk of a RASopathy, identifying the cause can help to take actions to improve the outcome of the disorder. Additionally, family members can be informed and encouraged to also get tested. Our genetic counsellors can provide medical advice.
You have a family history
You have a child with distinctive
facial features, heart defect
and/or developmental delay
You have a clinical diagnosis
of a RASopathy
POSSIBLE OUTCOMES OF THE TEST
A molecular genetic diagnostic report outlining the results of the sequencing analysis is provided. Changes in DNA sequences (variants) can be detrimental and lead to the development of a cardiac or aortic disorder, including asymptomatic disorders that develop later in life. We will report pathogenic and likely pathogenic variants as well as variants of unknown significance.
Pathogenic and likely pathogenic variants mean the genetic cause of the observed symptoms has been identified and may help determine the right treatment and management plan.
Variants of unknown significance means there was not enough evidence to classify the variant as either pathogenic or neutral. Annual variant reclassification and testing family members is recommended.
It is important to note that a negative result does not guarantee the absence of a disorder or that the disorder does not have a genetic cause. Genetic testing is an evolving field and may not detect all variants or there may not currently be enough evidence to classify all variants that lead to an inherited disease.