Vascular anomalies in PHTS

Introduction

People with PHTS can develop problems with blood or lymph vessels (which can be thought of as a waste collection system) called vascular anomalies (VAs). Research suggests that approximately 30–50% of people with PHTS are affected, although the true number is unknown and the severity can vary significantly from person to person. In people with PHTS, VAs are usually first seen in infancy or childhood. In some cases, VAs can cause serious health issues, and when very severe, can be life-threatening. 

Researchers are working to better understand why VAs develop in first place and how they change over time. PTEN Research is currently supporting three projects that study these questions. The projects will utilise data and samples collected from people with PHTS VAs and use laboratory models of PHTS VAs.

The goal of this work is to improve how these conditions are diagnosed and treated. Ultimately, this research aims to turn scientific discoveries into better care and a higher quality of life for people living with PHTS and VAs.

Project 1 goals

This study aims to create a classification system (a way to name and group VAs) for PHTS VAs.

Project 1 overview

There is a limited amount of information available about VAs in PHTS. This is a problem as it makes it more difficult to identify the right participants for potential future clinical trials. It also means that it’s difficult to know exactly which aspects of a person’s VA may improve with treatment and therefore makes it challenging to decide what improvement to look for in clinical trials. Experts also think that the VAs in PHTS are more complex in their presentation compared to other types of VAs caused other genetic changes.

In this retrospective study (looking back at past records), the researchers will examine medical records, scans and tissue reports from people with PHTS and VAs across multiple countries to describe exactly how their VAs look on medical imaging and under the microscope.

Project 2 goals

The types of VAs seen in people with PHTS can vary from one person to another. Not all PHTS VAs start in the same way or develop in the same pattern over time. Some affect specific types of blood vessels like capillaries, veins, or lymph vessels, while others involve a combination, such as both arteries and veins. 

This study aims to understand why VAs vary so much between people with PHTS and how these VAs start and develop over time.

Project 2 overview

The research group has previously discovered genetic changes associated with VAs in a type of cells in the blood vessel walls called endothelial cells. 

In this project, the researchers will use laboratory models and tissue samples from people with PHTS to look at other types of cells to identify which types of cells in the blood vessels are responsible for different VAs. They will also explore whether external factors (for example, environment or other health issues) may affect how VAs grow and whether having both tumours and VAs affects outcomes.

Project 3 goals

This project will investigate if VAs develop when a variant of the PTEN gene, which is present in every single cell of a person with PHTS following fertilisation of the embryo, is combined with an additional genetic change which may occur later in life - a so called ‘second hit’.

Project 3 overview

In this study, genetic testing of tissue samples from approximately 42 people with VAs or other lesions and confirmed or suspected PHTS in Australia will be undertaken

The study will use sensitive testing methods to discover changes in DNA within 138 genes linked to VAs or cancers.