What is the history of Megalencephaly Capillary Malformation Polymicrogyria Syndrome (mcap)?

Megalencephaly Capillary Malformation Polymicrogyria Syndrome (MCAP) is a rare genetic disorder that affects the development of the brain and blood vessels. It is characterized by several distinct features, including an enlarged brain (megalencephaly), abnormal blood vessels (capillary malformations), and a specific brain malformation called polymicrogyria. MCAP was first described in medical literature in 2012 by Mirzaa et al.

Megalencephaly refers to an abnormally large brain size. In individuals with MCAP, the brain is larger than normal due to an overgrowth of brain cells. This can lead to various neurological symptoms, such as developmental delay, intellectual disability, seizures, and muscle weakness. The exact cause of megalencephaly in MCAP is not fully understood, but it is believed to result from abnormal cell proliferation and increased cell size during brain development.

Capillary malformations, also known as port-wine stains, are birthmarks caused by abnormal blood vessels near the surface of the skin. In MCAP, these capillary malformations can be extensive and affect large areas of the body. They typically appear as pink or red patches and can vary in size and shape. Capillary malformations in MCAP are thought to result from abnormal development of blood vessels during embryonic development.

Polymicrogyria is a brain malformation characterized by an excessive number of small, irregular folds (gyri) on the surface of the brain. In MCAP, polymicrogyria is often seen in specific regions of the brain, such as the frontal and parietal lobes. This abnormal brain structure can contribute to the neurological symptoms observed in individuals with MCAP.

MCAP is caused by mutations in the PIK3CA gene. The PIK3CA gene provides instructions for making a protein called phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform. This protein is involved in regulating cell growth and division. Mutations in the PIK3CA gene result in overactivation of the protein, leading to abnormal cell proliferation and tissue growth, particularly in the brain and blood vessels.

MCAP is considered a sporadic condition, meaning it typically occurs in individuals with no family history of the disorder. Most cases of MCAP are caused by de novo mutations, which means the mutation arises spontaneously in the affected individual and is not inherited from their parents. However, rare cases of MCAP have been reported in families with multiple affected individuals, suggesting a possible autosomal dominant inheritance pattern.

The diagnosis of MCAP is based on clinical features, such as megalencephaly, capillary malformations, and polymicrogyria, as well as genetic testing to identify mutations in the PIK3CA gene. Imaging studies, such as magnetic resonance imaging (MRI), are often used to evaluate brain abnormalities and guide diagnosis.

Management of MCAP is focused on addressing the specific symptoms and complications associated with the disorder. This may include early intervention and therapies to support developmental delays, antiepileptic medications to manage seizures, and surgical interventions for certain complications. Regular monitoring and follow-up care are essential to address the evolving needs of individuals with MCAP.

In summary, Megalencephaly Capillary Malformation Polymicrogyria Syndrome (MCAP) is a rare genetic disorder characterized by megalencephaly, capillary malformations, and polymicrogyria. It is caused by mutations in the PIK3CA gene and typically occurs sporadically. Early diagnosis and appropriate management can help improve the quality of life for individuals with MCAP.