In June 2012, the discovery of the genetic mutation responsible for M-CM was published and the first set of clinical management guidelines was included in a supplement. The authors acknowledge that these guidelines are provisional and will surely change as understanding about M-CM grows. Note that this paper refers to M-CM as MCAP.
- A direct excerpt of the management guidelines [PDF]. Patients may find it helpful to provide this document to their doctors.
- The full supplement as a PDF The clinical management guidelines begin on page 26.
- The gene discovery paper, now Open Access in PubMed Central: De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes
The guidelines summarized:
- Clinic evaluations no less than every 6 months for the first ~6 years of life, and at least yearly thereafter. Special attention should be paid to a possible elevated risk of cancer and neurological symptoms. Follow up testing should be administered for any positive symptoms reported or exam findings.
- Baseline brain and spinal cord MRI imaging at the time of diagnosis. Repeat brain MRI every 6 months from 0-2 years and every year from 2-6 years. The need for imaging in older patients depends on prior findings and clinical course.
- Kidney cancer (Wilms tumor) screening following the guidelines for Beckwith-Wiedemann syndrome: renal ultrasounds every 3 months to age 8 years. The AFP blood test indicated for Beckwith-Wiedemann syndrome to detect hepatoblastoma (liver cancer) is not recommended at this time -- there have been no reported cases in M-CM.
- Baseline echocardiogram and electrocardiogram with a pediatric cardiologist to evaluate for cardiovascular malformations and rhythm abnormalities.
- Baseline thrombophilia evaluation.
Prior to this publication, there was little consensus among researchers about the need for cancer screening in M-CM. There is no new evidence about cancer incidence in M-CM, but the gene mutation that is now thought to cause M-CM, PIK3CA, is found mutated in cancer. Additionally, PIK3CA has recently been implicated in CLOVES syndrome, where a Wilms tumor risk has been more clearly demonstrated.