What is Megalencephaly Capillary Malformation Polymicrogyria Syndrome (mcap)

Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome (MCAP) is a rare, overgrowth disorder characterized by an abnormally large brain (megalencephaly) and vascular abnormalities, often accompanied by complex brain malformations. Currently, 23 people with Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome have shared their experiences on DiseaseMaps.org, highlighting the importance of community connection in navigating this complex condition.

What causes Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome?

MCAP is caused by somatic mutations in the PIK3CA gene. Unlike hereditary conditions passed from parent to child, these mutations occur spontaneously after conception, meaning they are mosaic—present in some cells but not all. This genetic mechanism leads to the overactivation of the PI3K-AKT signaling pathway, which regulates cell growth, division, and survival, resulting in the characteristic tissue overgrowth seen in Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome.

What are the primary clinical features of MCAP?

The clinical presentation of Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome varies significantly between individuals. Common features include:

• Megalencephaly: Enlargement of the brain, often present at birth.


• Capillary Malformations: Pink or reddish skin patches (port-wine stains) often found on the face, limbs, or trunk.


• Polymicrogyria: Abnormal folding of the brain's outer surface, which may lead to developmental delays or seizures.


• Body Asymmetry: Overgrowth of specific limbs or body segments.


• Connective Tissue Issues: Increased joint laxity or soft tissue thickening.

How common is Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome?

MCAP is an extremely rare disorder. While exact prevalence numbers are difficult to calculate due to underdiagnosis and the spectrum of severity, it is estimated to affect fewer than 1 in 100,000 individuals worldwide. The condition affects both males and females equally, and there is no known geographic or ethnic predisposition.

How is MCAP differentiated from other overgrowth syndromes?

Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome is frequently compared to other PIK3CA-related overgrowth spectrum (PROS) disorders. It is distinct because of the specific combination of brain enlargement, cortical malformations like polymicrogyria, and widespread capillary malformations. Unlike syndromes caused by germline mutations, MCAP is typically not inherited, which differentiates it from many other genetic neurodevelopmental disorders.

Next steps

• Consult a clinical geneticist to discuss molecular testing and the mosaic nature of the condition.


• Coordinate care with a multidisciplinary team, including neurologists, dermatologists, and physical therapists.


• Join the DiseaseMaps.org community to connect with other families navigating the challenges of Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome.

Medical disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment.

References

• NIH Genetic and Rare Diseases Information Center (GARD): MCAP syndrome overview.


• Orphanet: Megalencephaly-capillary malformation-polymicrogyria syndrome (ORPHA:261244).


• OMIM (Online Mendelian Inheritance in Man): Entry #603387.


• The PIK3CA-Related Overgrowth Spectrum (PROS) foundation resources.