Pictured above, from left to right: Prof. Steve Jeffery, Dr. Pia Ostergaard, Prof. Peter Mortimer, Prof. Sahar Mansour, Dr. Silvia Martin Almidina, Glen Brice, Dr. Kristiana Gordon

Introduction of the Primary Lymphedema Gene Panel
Pia Ostergaard, John Short, Uruj Anjum, Kristiana Gordon, Peter Mortimer, Sahar Mansour

We know that there are two ‘types’ of lymphedema (spelled lymphoedema in the UK); one which occurs when a previously healthy lymphatic system is damaged, maybe because of cancer treatment or infection, which we call ‘secondary lymphedema’. The other type occurs because of a genetic fault causing underdevelopment or weakness in the lymphatic system, which we call ‘primary lymphedema’. 

Recent advances have shown that there are several different forms of primary lymphedema. At St George’s University Hospitals NHS Foundation Trust, there is an ongoing research study called LYMRES. This is working to discover the faults in the genes involved in primary lymphedema and how those faults affect the functions of the lymphatic system. The research team consists of dermatologists, geneticists, genetic counsellors and laboratory scientists.

So far, we have recruited over 600 patients since work began in 2006 which makes it the biggest study of its kind in the UK. The team are doing amazing work and over the past 10 years have already managed to identify eight NEW genes which are involved in lymphatic development.

The first of the genes identified were those that play a role in Milroy disease (VEGFR3) and Lymphedema distichiasis syndrome (lymphoedema associated with extra eyelashes arising from the inner eyelids) (FOXC2).   Through subsequent research, several new genes associated with primary lymphedema have been identified including CCBE1, GJC2, GATA2, KIF11, VEGFC, and more recently PIEZ01 and EPHB4.  When they work properly, these genes are crucial for the development of normal lymphatics. When there is a fault in one of these genes the patient develops lymphoedema.

Until recently, testing for these genes has been limited. We were only able to test these genes one by one and not all of them were available in the diagnostic laboratory.  St George’s DNA diagnostic laboratory have introduced a new gene panel for primary lymphedema. This is able to look for mistakes in all of the 12 genes known to be associated with primary lymphedema with results available in just 8-12 weeks.   This will enable doctors to give an accurate diagnosis for many more patients with primary lymphedema. 

For now, this information doesn’t change how we treat and care for most patients with primary lymphedema. However, some of these conditions may be associated with other problems that we can look for (e.g. kidney or heart problems) and having an accurate genetic diagnosis means we can predict the risk to relatives of developing similar problems.  Simply knowing ‘why’ can help many of those affected. 

The science is moving fast and what is being learnt will be invaluable in the future. Whilst not directly in the field of lymphology, research is underway in several countries into the feasibility of various gene repair systems where damaged DNA is replaced or corrected and there is even talk that stem cell transplants may be able to be used to treat some forms of genetic disease in the future.

These are exciting times and while progress may seem slow there is much more to learn and there is real hope that an accurate diagnosis will lead to much better, targeted treatment and a brighter future for those with primary lymphedema.