Hensin Tsao, MD, PhD
In the world of dermatology, we are filled with hamartomatous “overgrowth” syndromes. Many, however, are de novo so the genetic mechanism is unclear. Often times, segments or large quadrants of the body are affected clinically suggesting somatic mosaicism.
Two studies in 2012, that complimented some earlier studies, looked at somatic mosaic mutations of these various overgrowth syndromes. In the first study, megacephaly was a feature in all three cases. Patients may have nevus flammeus. The blood/saliva from all patients was subjected to total exome resequencing, which is a technology that is really hitting medicine right now. In effect, total exome resequencing is looking at all of the coding sequence of one’s genome (exome) and in doing so, trying to find the mutation that may be responsible for the phenotype that you see. In the first study, megacephaly was a feature in all three cases. Patients may have nevus flammeus.
The three genes that were found were the AKT3, PIK3R2, and PIK3CA.
- Germline and mosaic versions of cancer mutations lead to developmental and hamartomatous conditions
- As sequencing technologies improve, the mechanism of new syndromes will emerge
- Interesting that these patients may not be more susceptible to cancer overall
- Between biologics and small molecule inhibitors, we are in a new therapeutic renaissance
- The mechanism-to-medicine bridge is finally open
- NextGen sequencing will help define rare hereditary and mosaic genodermatoses
- Health care economics, not science, is the wild card