Researchers have identified the genetic mutation that occurs before birth responsible for the development of Sturge-Weber syndrome and port-wine birthmarks. Pinpointing the genetic cause behind this rare disorder and a common birthmark has been described by experts as “a major breakthrough”.
The study, published in the New England Journal of Medicine, explains the mutations responsible for Sturge-Weber syndrome and port-wine birthmarks, which could pave the way for future treatment options.
Co-senior study author, Anne Comi, M.D., Director of the Kennedy Kriegar Institute’s Hunter Nelson Sturge-Weber Center, said:
“This is a complete game changer for those with Sturge-Weber syndrome and the millions born with port-wine birthmarks. Now that we know the underlying genetic mutation responsible for both conditions, we’re hopeful that we can move quickly towards targeted therapies, offering families the promise of new treatments for the first time.”
Birthmarks are very common, occurring in nearly 10% of all infants at birth or a few weeks after they are born. Many birthmarks are harmless and pose no health threat. However, it is very important to determine the type of birthmark and whether it poses any potential risks in the future.
About 1 in every 1,000 babies are born with port wine stains – birthmarks caused by abnormally dilated capillaries in the skin resulting in reddish to purplish discoloration of the skin (similar to the color of port wine).
Physicians can perform laser treatment to remove port-wine birthmarks in infant children, however, there is a high chance of recurrence.
Children born with a port wine stain have around a 8% to 15% risk of having Sturge-Weber syndrome.
Sturge-Weber syndrome, also known asencephalotrigeminal angiomatosis, encephalofacial angiomatosis, or Sturge-Weber-Dimitri syndrome, is a neurological and skin disorder that experts thought was congenital*. The syndrome is associated with numerous health problems and can cause seizures, weakness of the body, glaucoma, and developmental delay.
Treatment options for the syndrome remain limited; medications currently available may help with some symptoms, such as reducing the frequency and severity of seizures and treating glaucoma.
Co-senior study author, Jonathan Pevsner, Ph.D., Director of Bioinformatics at Kennedy Krieger Institute, said:
“This study presents a turning point for research on Sturge-Weber syndrome and port-wine birthmarks. While we suspected that a somatic mutation* was the cause for decades now, the technology to test the theory didn’t exist. The advancements in whole genome sequencing and the development of next-generation sequencing tools finally allowed my lab to test and prove the hypothesis.”
Using affected and unaffected tissue as well as blood samples from three individuals with SWS, the team were able to carry out a complete genome sequence and identify the somatic mutation responsible for the syndrome and the birthmarks.
A nucleotide transition in gene GNAQ on chromosome 9q21 was identified in all three of the affected samples.
They confirmed their finding by conducting a separate analysis which showed that 23 out of 26 samples from people with SWS and 12 out of 13 from people with port-wine birthmarks had the same mutation. No such mutations were found in the control samples.
Surprisingly, the gene that’s responsible for SWS is also associated with a type of melanoma of the eye, called uveal melanoma.
GNAQ is responsible for encoding a set of membrane proteins that make sure the pathways within the cells are working normally. In SWS and port-wine stains a mutation of GNAQ occurs which results in abnormal activity, causing both of the conditions.
The researchers believe their findings will help scientists develop new medications that selectively inhibit the pathways that lead to port-wine stains and SWS.
The President and CEO of the Sturge-Weber Foundation, Karen Ball, said:
“As I look back on 25 years of research into Sturge-Weber syndrome, this is a momentous advancement that is thrilling as both an advocate and parent of an affected child. This breakthrough gives renewed hope to my family and thousands of others, and brings new opportunities to increase the pace of scientific discovery for Sturge-Weber.”
The discovery that SWS is caused by a somatic mutation means that the syndrome is not inherited, which has been a major concern for many parents.
* Definitions of some words use in this article:
- – Congenital – means you are born with it.
– Somatic mutation – a change in DNA that occurs after conception, i.e. it is not inherited
Written by Joseph Nordqvist