Genetic Mutations in PIK3CA Identified as Cause of M-CM

The discovery of the genetic mutation that causes M-CM was published on June 24th by a team of researchers led by Dr. William Dobyns.  The mutated gene is PIK3CA and as previously hypothesized, the mutations were found to be postzygotic mosaic mutations.  This means the mutation occurs after cell division begins -- it explains the high degree of variability in severity of M-CM characteristics and the absence of familial inheritance.

PIK3CA is a gene that is known to be mutated in various cancers, and as a result is already being studied as a target for drug treatment.  Because of PIK3CA's association with cancer, the team of researchers who discovered the gene have published new care recommendations that include abdominal ultrasound screening for Wilms' tumor and encourage those caring for individuals with M-CM to be aware of the possibility of an elevated cancer risk in those with M-CM.   We have added a summary of these new management guidelines in the Resources section of our website, the full text can be downloaded here.

Please note that in both the gene discovery paper and the supplement with management guidelines, the authors refer to M-CM as MCAP.

For families interested in genetic testing to clarify diagnosis, there is not yet a clinical genetic test available to detect these mutations.  Testing may be available via research teams, including Dr. Dobyns' lab. We suggest that you share this paper with your geneticist to determine the best course of action.

Within a month prior to this publication, two other research teams have published discoveries involving mosaic PIK3CA mutations causing overgrowth syndromes distinct from M-CM. One of these syndromes is CLOVES, which has a more clearly demonstrated risk of Wilms tumor.  These two papers are:
Somatic Mosaic Activating Mutations in PIK3CA Cause CLOVES Syndrome.
Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA.

We hope to post additional information about the significance of this genetic discovery in the near future.