Segmental overgrowth – printed with the permission of Mandy Sellars from her website
Mandy writes – Back in 2012 I was a patient at Addenbrookes hospital in Cambridge where two amazing doctors, Dr Robert Semple and Dr Vicki Parker had been researching my condition using DNA sequencing. Their result was utterly amazing and something that I never thought would happen in my lifetime. They had found the faulty gene that causes the overgrowth in my legs and feet, which also indicated that my upper body is not affected by this gene mutation. This turned out to be a single letter mutation in the PIK3CA gene. I was the first person in the world to be discovered with this exact gene mutation, which is something that I am extremely proud to say.
What follows is information from my doctors in to Segmental Overgrowth which includes the PIK3CA mutation:
What is segmental overgrowth?
Segmental overgrowth describes a condition where there is an excess of growth in different parts of the body, but normal growth elsewhere. Examples of this include:
· PIK3CA related overgrowth spectrum (PROS)
· Congenital lipomatous overgrowth, vascular malformations, epidermal naevi and skeletal abnormalities (CLOVES)
· Macrocephaly-capillary malformation (M-CM)
· Proteus syndrome
· Klippel-Trenauney Syndrome (KTS)
What causes segmental overgrowth?
Segmental overgrowth disorders have recently been shown to be caused by changes in genes (genetic mutations) which cause key growth signals in cells to be switched on all of the time. The genes in which these mutations have been found include;
Is this an inherited condition?
These conditions are not inherited in the usual way from parents, and are equally not passed onto children. A genetic mutation occurs early on in pregnancy in a single cell when the foetus is just a tiny ball of cells. As just one cell is affected at this time, only some parts of the body are affected, whilst other parts grow normally. The genetic mutation occurs because the cell makes a mistake in copying DNA when dividing to create a new cell; there are no known in utero triggers for this.
Will the overgrowth ever stop?
In some patients, overgrowth continues into early adulthood and then slows down or stops, but in others, growth continues into adult life. At present there is no way of predicting whether someone will keep growing or not, but research efforts are underway to answer this question.
Is there an increased risk of cancer?
Many of the genetic mutations found in segmental overgrowth conditions are also found in cancers. However, cancers have lots of different genetic mutations and current scientific evidence suggests that the gene changes found in segmental overgrowth do not trigger cancer. The current reported rate of cancers is low in patients with segmental overgrowth, however future research studies are needed to determine the true risk, and in the meantime, your doctors will monitor you or your child closely for this.
Are there any available treatments?
At present the main treatment for overgrowth is surgical removal of tissue, or operations to slow down growth. However, finding the genetic cause of these conditions has opened up the possibility of treatments with drugs that may be able to stop or slow down overgrowth. If you or your child is severely affected, your doctor may discuss with you a treatment called sirolimus (rapamycin) or everolimus. These drugs help to slow growth in cells, and there is a small amount of evidence to suggest these may help in some forms of segmental overgrowth.
We are currently setting up a trial in patients with PIK3CA related overgrowth (PROS) to see if sirolimus is better than sugar tablets (placebo) at reducing overgrowth. If you are interested in treatments or wish to know more about our trial please email:Overgrowthstudy@medschl.cam.ac.ukand you can check our clinical trials page for more details.
How do I get myself or my child tested?
As part of our research study, we can test for the gene changes commonly found in segmental overgrowth conditions, and can be contacted directly to organise this via our email address: Overgrowthstudy@medschl.cam.ac.uk. Alternatively, you can discuss testing with your GP or local doctor. In order to test, doctors will need to look at DNA taken from an affected area of overgrowth, and this may require taking a small sample of skin (skin biopsy).
You can also take a look at the Facebook and Twitter pages for more information: twitter.com/OvergrowthStudy facebook.com/segmental.overgrowthstudy
Proposals for super specialised clinic for segmental overgrowth disorders
I was invited to attend a meeting with Dr Rob Semple and Dr Victoria Parker from Addenbrookes Cambridge.
Other attendees were Miss Rachel Knox, Ms Leena De Silva and Mr Graeme Clark from Cambridge, Professor Peter Mortimer, Dr Sahra Mansour and Dr Glenn Brice from St George’s Hospital, London, Dr Veronica Kinsler, Dr Anna Matinez, Dr Lindsay Shaw from GOSH and Professor Jill Clayton-Smith from Manchester.
Patient Support Groups represented were Mandy Sellars and Sue Harper for GoPI3Ks, Ms Lorraine Yeomans and Ms Julia Higgins from M C-M.net and Jean Harrison and Sarah Gardiner from the Proteus Family Network.
The meeting discussed proposals for setting up regional clinics for segmental (mosaic) overgrowth disorders including those mentioned in the information from Mandy Sellars.
We discussed locations of these clinics and the most likely locations are London, Manchester and Cambridge.
The support groups that attended were asked to survey their members in order to influence and support the clinic proposals that were going to the NHS. We need to demonstrate that these clinics will not require additional funds and may actually save the NHS money. Some of you will have received surveys and thank you to those who returned these. The results have been passed on to Cambridge and we await the results.