PIK3CA-related segmental overgrowth
PIK3CA-Related segmental overgrowth includes three distinct but related clinical manifestations: Fibroadipose Hyperplasia (FH); CLOVES syndrome and Megalencephaly-Capillary Malformation (MCAP). These disorders are all due to a change in the gene PIK3CA. The genetic change in PIK3CA is only in certain cells of the body and is usually not seen in the blood. Which body parts are affected is determined by which cells in the body have the genetic change in PIK3CA.
Fibroadipose hyperplasia (FH) manifests as patchy overgrowth of a limb or part of the body. The overgrowth is due to fatty, fibrous and/or blood vessel overgrowth in a particular region of the body. This is usually not evident at birth and the overgrowth typically gets worse over time. The overgrowth is not malignant (i.e. not a cancer) but may cause health and medical issues. Typical issues may be problems walking due to the legs being a different length, problems moving a limb due to the overgrowth and challenges in regular daily activities due to deformity of a body part. Learn more about fibroadipose hyperplasia (FH)
CLOVES stands for Congenital Lipomatous assymetric Overgrowth, Vascular malformations, Epidermal nevi and Skeletal and spinal anomalies. This is similar to fibroadipose hyperplasia (FH) with more prominent blood vessel overgrowth, nevi (moles) and bone and spine problems. This condition may be noted on prenatal ultrasound or at birth. This may also progress with time. There may be life-threatening problems due to the overgrowth pushing on vital organs or because the increased blood vessel growth can lead to heart failure. Learn more about CLOVES syndrome
Megalencephaly-capillary malformation (MCAP) syndrome is characterized by overgrowth of all or part of the head and brain as well as overgrowth of other body parts as is seen in fibroadipose hyperplasia (FH). The overgrowth of the brain causes problems with brain function which may lead to seizures, low muscle tone, developmental delays and intellectual disabilities. Involvement of other body parts may also cause health and medical issues as described for fibroadipose hyperplasia (FH), above. These findings may be seen on prenatal ultrasound in some cases whereas in other cases it is diagnosed at birth or in childhood. Learn more about MCAP syndrome
The diagnosis may be suspected based upon physical examination and x-ray studies, such as Magnetic Resonance Imaging (MRI), Computated Tomography (CT) scan, ultrasound, etc.. Confirmation of the diagnosis should be done by DNA testing of PIK3CA from tissue from an affected body part.
Clinical exam. The physical examination includes monitoring overgrowth of body parts as well as assessments of function. For CLOVES, monitoring heart function may be important if there is significant blood vessel overgrowth. Monitoring development and looking for seizures is important for children with MCAP.
Imaging. Imaging studies are often important to assess and monitor areas of overgrowth. No one type of imaging is best for everyone with PIK3CA-related overgrowth. Some individuals may even need multiple types of imaging studies to look at different body parts or different types of overgrowth (fatty overgrowth, blood vessel overgrowth, etc.).
Pathology. The PIK3CA gene regulates growth of cells in the body. The genetic changes in this gene causes the cells that have the change to grow too much and also may cause certain types of cells/tissues to grow in the wrong place.
Genetics. The genetic change in PIK3CA is often only seen in cells of affected body parts and not in the blood. A biopsy from an area of overgrowth should be obtained for DNA testing to confirm the diagnosis.
Because these disorders are highly variable, treatments may also vary between individuals. Your doctors will talk with you about what treatment, if any, is best for your child. Possible treatments may include surgeries to remove overgrown tissues, if this is causing problems. Vascular (blood vessel) procedures may be needed to close off overgrown blood vessels if this is causing problems with bleeding, low levels of blood cells or problems with heart or other organ function. Medical therapy with medications that target the genetic defect may be offered in complicated cases as part of a clinical trial.