When Mandy was born, her upper body was extremely thin whilst her legs and feet were much larger than an average baby’s limbs. The doctors that examined Mandy didn’t know what had caused the issue but suggested it might be a rare form of Proteus Syndrome.
In 2011, Mandy was introduced to two researchers from Cambridge University Hospitals (CUH), Dr Robert Semple and Dr Victoria Parker. After many months of blood tests, scans and skin biopsies the research team discovered that Mandy had a mutation in one of her genes known as PIK3CA. “I never thought this day would come” says Mandy, “the researchers had found out what caused my condition! I was the first person in the world to have been found with this specific gene mutation.”
Mandy agreed to take part in a NIHR CRN clinical trial led by the CUH team called ‘Genetic and Physiological Investigation of Patients with Rare Segmental Overgrowth Disorders, Lipoblastomas or Hemihypertrophy’.
The trial was testing an existing drug, Rapamycin, which was originally developed for kidney transplant patients. Early testing in the laboratory on cells grown from skin biopsies showed the drug could intercept the signal that caused the overgrowth. There was never any doubt in Mandy’s mind about whether she would take part in the trial as she says, “I had to take (the drug) to see what would happen.”
After taking Rapamycin for four years, Mandy’s legs have begun to shrink. “Dr Semple and Dr Parker have saved my life! My legs are shrinking and I’ve lost five stone in weight. I am finding moving around so much easier now of course. Before I took part in the trial I was facing the likelihood that I would become permanently bed bound. Now I know that one day I will be able to go out on my own again!”
“My parents were so relieved to finally have an answer about the cause of my overgrowth after all these years! I am so glad that I took part in this study. If I hadn’t given it a go I would have always been saying to myself, ‘What if?’”
“I hope that my involvement in this research will help other people with overgrowth syndrome, particularly those people with PIK3CA Related Overgrowth Spectrum. If anyone has the chance to take part in a clinical trial I would say to them ‘Do it! What have you got to lose?’”
It is Mandy’s enthusiasm for taking part in the Investigation of Segmental Overgrowth study that remains crucial to the future exploration of rare overgrowth disorders, where not all parts of the body are affected, as Dr Robert Semple, Wellcome Trust Senior Research Fellow and Honorary Consultant Endocrinologist explains:
“Different people have very different severities of problem even with the very same gene change. A key aim of our studies is to gather better information about the long term outlook so that we can offer the most accurate advice to families, and so we can target new treatments to those who need them most.”
“There is no quick way to answer this need. Instead it relies on gathering information from as many patients as we possibly can, on continuing to follow their progress as time passes, and on swapping notes with researchers and doctors in other countries who see many similar patients.”
The Investigation of Segmental Overgrowth study, led by Cambridge University Hospitals NHS Foundation Trust, investigates patients with any form of segmental overgrowth, hemihypertorphy or lipoblastomas from a genetic and physiological viewpoint. When the study team identifies new genetic variants, patients are invited to participate in further phenotyping studies (studies where researchers attempt to define the full characteristics of a person’s genes) aimed at improving understanding of their condition, informing decisions about therapy, and giving insights into cellular growth control and metabolism.
Mandy is helping to provide support for other people with Segmental Overgrowth via the website she has created at www.gopi3ks.com. She also tells her story in more detail on her personal website www.mandysellars.com
Find out more about the Segmental Overgrowth Study at www.overgrowthstudy.medschl.cam.ac.uk