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Genetics

A June 2012 journal article reports that M-CM is caused by a mutation in a gene called PIK3CA.  This mutation was found in 23 individuals with M-CM. In most cases, the mutation was the result of somatic mosaicism. This means that the mutation occurred after cell division had begun and was not inherited.  In two cases, the mutations were thought to be germline mutations. There are no reported cases of M-CM running in families.  There are no reported cases of individuals with M-CM that have reproduced, so it is unknown if M-CM could be inherited under this circumstance.

PIK3CA mutations were recently implicated in another overgrowth syndrome called CLOVES, where the mutation also is found in a mosaic state.  There is some symptom overlap between the two syndromes, but they also have enough differences to distinguish them from each other in most cases.  The full significance of this relationship is not understood at this time.

PIK3CA is also found mutated in human cancers.  Previous to this genetic finding, the need to screen for kidney cancer (Wilms tumor) and hepatoblastoma (liver cancer) was controversial in M-CM.  The researchers that published this new genetic finding are now recommending Wilms tumor screening for M-CM patients as well as a heightened awareness of a possible elevated cancer risk for clinicians caring for M-CM patients.