Macrocephaly Capillary Malformation (M-CM) or Megalencephaly Capillary Malformation (MCAP) is a complex overgrowth syndrome that is caused by a genetic mutation in the PIK3CA gene.
How does M-CM occur?
M-CM is not usually inherited from a child’s parents, the mutation in the PIK3CA gene happens spontaneously in a cell during early cell division after conception. The cells then continue to divide and some cells within the body will have the mutation and other cells will not, this mixture of cells with and without the genetic mutation is known as mosaicism.
How does M-CM affect individuals?
People with M-CM usually have a range of challenges that can include both physical and cognitive developmental delays, the severity of which can vary greatly from individual to individual.
Common features of the syndrome include macrocephaly (caused by overgrowth of the brain), body asymmetry (caused by some parts of the body growing at a faster rate than others), low muscle tone, lax joints, learning difficulties and other neurological problems such as seizures and brain abnormalities
How does the mutation cause overgrowth?
The PIK3CA gene provides instructions for making the p110α protein which plays an important role in cell growth and cell division. Mutations in the PIK3CA gene cause an altered p110α protein to be produced, this makes cells continuously grow and divide. This increased cell growth is what leads to the overgrowth that is seen in M-CM.
How rare is M-CM?
M-CM is very rare, medical literature reports 150 cases worldwide, however it is likely that there are more individuals with the syndrome that do not have a diagnosis.
In practical terms the rarity of the syndrome means that not only is there great variability in the knowledge and understanding of the syndrome amongst doctors and other health professionals but also in the ease at which patients can access testing, monitoring and therapy to help with the condition.