Characteristic features are an overgrowth of the brain (megalencephaly or hemimegalencephaly) with corresponding neurological symptoms in combination with capillary malformations (CM).
MCAP is predominantly sporadic (not familial). It is caused by activating mutations in the oncogene PIK3CA, usually present as a somatic mosaic. Few cases with presumed inherited mutation have been described so far. The mutation causes overactivation of the PI3K (phosphatidylinositol 3-kinase)/AKT/mTOR pathway.
The overgrowth may affect the entire brain (megalencephaly) or regionally affect one half of the brain (hemimegalencephaly) and is associated with macrocephaly (head circumference > +3 SD). In addition, a relatively mild overgrowth (subcutaneous tissue thickening) in the sense of hemihyperplasia is usually found in one lower limb. At birth, weight and length are usually above +3 SD.
Capillary malformations (CM) occur, on the one hand, in the form of extensive nevi with a mesh-like reticular erythematous pattern (livedo reticularis or CMTC); on the other hand, as facial nevi flammei, especially in the area of the philtrum and/or lips.
Neurological symptoms: muscle hypotonia, psychomotor retardation/mental retardation mostly to a mild degree, rarely (in about 10%) to a severe degree, epilepsy.
Other structural CNS changes: In addition to megalencephaly or hemimegalencephaly, other CNS abnormalities may be present such as dilated ventricular system, dilated dural venous sinuses, dilated Virchow-Robin spaces, increased white matter signal intensities in T2-weighted MRI, focal cortical dysplasia as well as polymicrogyria, cerebellar tonsil depression, thickened corpus callosum, dilated optic nerve sheaths, and syringomyelia.
On the hands and feet, there are clustered syndactyly of the toes, especially 2–3, rarely 3–4 or 2–4, and of the fingers 3–4. In addition, there is an increased distance between the big toes and the 2nd toes (sandal gap) and rarely postaxial polydactyly.
Tumors: Mainly circumscribed adipose tissue hyperplasia/lipomatosis/lipomas. In addition, meningioma, Wilms tumor, leukemia, medulloblastoma in about 2–3% of patients.
In addition: cardiovascular malformations, arrhythmias.