Identification of genetic mutation linked to complications associated with common birthmarks

Research led by BRC-supported Dr Veronica Kinsler has found that a subset of a common type of birthmark, which is associated with severe complications, is caused by activating mutations in the genes GNAII and GNAQ. These findings could lead to early identification of infants at risk of serious complications.

Dermal melanocytosis (also known as Mongolian blue spots) are common birthmarks, and are often dismissed as a normal finding. When they co-occur with vascular birthmarks they come under the diagnostic heading of phakomatosis pigmentovascularis (PPV), a condition considered previously to be a separate phenotype. 

Occassionally Mongolian blue spots and PPV can be associated with congenital glaucoma which can damage vision, and with vascular abnormalities in the brain which can lead to seizures and neurodevelopmental delay. Early detection of glaucoma and vascular abnormalities means treatment can be started sooner, reducing the risk of these complications. Research led by Dr Veronica Kinsler at the Great Ormond Street BRC offers a way for medical teams to determine which children with Mongolian blue spots are at risk of suffering complications.

This study found that extensive dermal melanocytosis and PPV are genetic conditions that are associated with post-zygotic mutations in the genes GNA11 and GNAQ. These mutations were undetectable in the blood, however were detected at very low levels in the affected tissue, suggesting that the disorder is caused by a post-zygotic mutation.

These disorders join a number of others – including Sturge-Weber syndrome (SWS) – in the group of mosaic heterotrimeric G-protein disorders. This leads the way for accurate clinical molecular diagnosis and identification of new-born babies at risk of complications associated with these birthmarks. It also allows investigation into potential therapeutic options for these patients.

The study findings were published in The Journal of Investigative Dermatology. The lead researcher on this paper was Dr Veronica Kinsler, a BRC-supported researcher. The research was supported by the Wellcome Trust.