A diagnosis of Marfan or Loeys–Dietz syndrome carries implications for the entire family. Although one quarter of cases emerge spontaneously, the remaining 75% are inherited directly from a parent. Consequently, other family members may be unwittingly (perhaps life-threateningly) affected.
The first person within a family to receive a confirmed diagnosis of MFS or LDS is known as the index patient or the 'proband'. They will undergo genetic assessment and testing with a blood test that tests for a panel of over 35 genes known to be responsible for these types of conditions. Within the NHS genetic test directory, the panel is known as R125. The aim is to identify the specific causative variant behind their condition. They will probably have endured a year-long wait to see the geneticist, and a further three months waiting for the results of the blood analysis.
If a variant has been identified, genetic testing should be offered to first-degree (biological) relatives, such as parents, siblings, and children. This process, known as cascade testing, expedites the diagnosis in other family members as the geneticist has the specific variant for comparison and does not need to test for the entire R125 panel.
Process
All first-degree relatives should be referred by their GP or consultant to their nearest clinical genetics service, accompanied by a copy of the index patient’s mutation report. (The report will arrive from the relative’s genetic centre). Importantly, they should be offered an echocardiogram to assess their aorta while awaiting assessment. This be done as a matter of urgency.
Understanding your condition means you can control it! It allows for medical management, which may include annual scans, lifestyle modifications, preventative medication and/or life-saving surgery.
