Mandy Sellars was born in Lancashire, England, in 1975, with a medical mystery that baffled every doctor she met. Soon after she was born, she was a medical mystery. From the waist up, she appeared completely normal, but from the waist down, her legs were abnormally large. By the time she was a toddler, her legs had grown disproportionately compared to the rest of her body. Despite extensive testing, doctors could not identify the cause. Doctors initially advised her parents to amputate her legs, but they dismissed it.
She walked independently in childhood, obtained a university degree and maintained an active lifestyle despite her condition.
Over the years, her condition caused her legs to grow to a combined weight of over 200 pounds, making even mobility a daily challenge. Mandy’s condition was initially believed to be a form of Proteus syndrome, the same disorder linked to Joseph Merrick, known as the “Elephant Man.” However, later genetic testing revealed this was not accurate.
In 2013, researchers discovered that Mandy’s symptoms were caused by a mutation in the PIK3CA gene, which regulates cell growth and division. Mandy Sellars became the first person worldwide to be diagnosed with a unique variant of PIK3CA‑Related Overgrowth Spectrum (PROS), following genetic sequencing that revealed a somatic mutation of the PIK3CA gene. This mutation leads to PIK3CA-Related Overgrowth Spectrum (PROS), a rare condition that causes abnormal and asymmetrical tissue growth in various parts of the body.
The PIK3CA mutation is somatic, meaning it occurs after conception and is not inherited. As a result, only certain tissues are affected, depending on where the mutation occurs in the developing embryo. According to the National Organization for Rare Disorders (NORD), PROS affects about 1 in a million people, and the severity varies widely from mild tissue overgrowth to extensive deformities.
In 2010, Mandy faced a life-threatening infection (Sepsis) due to deep vein thrombosis in her left leg. Doctors were forced to amputate the leg above the knee to prevent the infection from spreading. She expected the surgery to end years of pain and mobility struggles. However, within months, something unprecedented occurred, her amputated leg began to regrow.
Tissue and fat cells started multiplying again at the stump, leading doctors to confirm that her genetic mutation was still active. Her body continued to produce excess tissue as if it had ignored the amputation entirely.
In an effort to control the growth, Mandy agreed to try a targeted therapy using cancer medication, which inhibits the PI3K/AKT/mTOR signaling pathway, the same pathway affected by the PIK3CA mutation. Drugs like Sirolimus (Rapamycin) and Alpelisib (PIQRAY), typically used in cancer treatment, showed promising results by slowing or reversing abnormal tissue growth.
Within months of starting treatment, Mandy’s leg size began to reduce, marking one of the first successful uses of PI3K inhibitors in managing PROS-related conditions.
But the effects were short lived, after two years of providing results, the drugs stopped to have any effect on her.
Today, Mandy Sellars continues to live with the effects of PROS. She remains an active advocate for rare disease awareness, sharing her story to highlight the importance of genetic research, patient education, and compassionate medical care.
Recognising the need to raise awareness and support for individuals living with overgrowth disorders, she founded the charity GoPI3Ks in 2017. They continue to give support especially focussing on mental health issues faced by those living with PROS.
The organisation works internationally to advocate for patients with PROS, promote research into targeted therapies, and improve access to accurate diagnoses
Her case has been featured in numerous medical journals and documentaries, and it has helped researchers better understand how somatic mutations can lead to localized overgrowth syndromes.
(Rh/TL)