Researchers identify genetic link between lymphatic disorders and stillbirth

In a world-first discovery, South Australian researchers have identified a genetic mutation responsible for a lymphatic disorder that can cause stillbirth or serious chronic illness in affected children.

An abnormality in the development of lymphatic vessels in unborn children, resulting in fluid accumulation in the heart, lungs and other organs, has been discovered by scientists from the Center for Cancer Biology (CCB) based at the University of South Australia (UniSA) and Pathology SA.

The results are published today in the journal Science Translational Medicine.

Professor Natasha Harvey, director of the CCB, said a genetic study of six families affected by stillbirth or lymphoedema revealed the link between a gene coding for a mutated protein called MDFIC and the accumulation of fluid in the organs and vital tissues.

This demonstrated that MFDIC is important in controlling the growth and development of lymphatic vessels in the fetus for the first time.

The Cancer Biology Center collaborated with scientists and clinical teams from Women’s and Children’s Hospital, the University of Adelaide, Belgium, Germany, the United States and Iran to make this breakthrough.

“The lymphatic system is a network of vessels (pipes) and nodes (filters and control centers) important for maintaining water balance in our tissues and transporting infection-fighting white blood cells throughout our bodies,” explains the professor. Harvey.

We determined that MDFIC controls cell migration, an important early event in the formation of lymphatic vessel valves. The genetic variants we found in our study reveal a crucial, previously unrecognized role of MDFIC in the lymphatic vasculature. If the lymph valves do not form properly, lymph fluid builds up in critical organs such as the heart and lungs, causing major respiratory problems that can lead to stillbirth or chronic disease.

Professor Natasha Harvey, Director of the CCB

An SA Pathology research team led by Professor Hamish Scott first found the genetic link in an Australian family. Their international colleagues in Belgium, Germany and the United States have reported variants of the same gene, MDFIC, in several patients with the same lymphatic disorder.

Professor Harvey says the disorder, known as central conductive lymphatic anomaly (CCLA), is one of a group of serious lymphatic disorders and can lead to stillbirth or serious chronic illness in affected children.

Few effective treatments are available, but with the continued identification of the genetic causes of CALCs, Professor Harvey says the next step is to develop new therapeutic drugs to combat the disease.

“There are drugs that can be used to treat these disorders, but we need to make sure that the signaling pathway being addressed by these drugs is the same one that is affected in our patients.

“This project is about the power of collaboration locally, nationally and internationally, so that was very important. Science is done in teams and we have excellent research teams here in Adelaide at the Cancer Biology Centre. Our doctoral students and postdoctoral fellows have been an integral part of this work. They really motivated him and we are delighted to work with such a talented group of people.

World’s first discovery links lymphatic disorders to stillbirth

Video credit: University of South Australia


University of South Australia

Journal reference:

Byrne, AB, et al. (2022) Pathogenic variants of MDFIC cause recessive central conductive lymphatic abnormality with lymphedema. Science Translational Medicine.

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