PROS (PIK3CA-Related Overgrowth Spectrum)

Key Features

People with PROS may experience various symptoms, including:

Overgrowth of limbs, skin, or organs: Growth may be uneven, such as one arm or leg being larger than the other.
Vascular issues: Abnormal blood vessel growth can lead to hemangiomas (benign vascular tumors), lymphatic malformations, and other complications.
Facial or cranial abnormalities: Some individuals may have asymmetrical growth of the skull or face.
Other physical complaints: Potential problems include pain, fatigue, or difficulty moving, depending on the location and extent of the overgrowth.

Causes

PROS is caused by a change (mutation) in the PIK3CA gene. This mutation occurs randomly after conception and is not inherited from the parents. It is not a hereditary condition. The mutation is typically present in only a portion of the body’s cells, meaning that some tissues and organs have the mutation while others do not. This phenomenon is called “mosaicism.”

Diagnosis

The diagnosis of PROS is based on physical features and genetic testing to confirm the PIK3CA mutation. A specialist often uses imaging techniques (such as MRI) and genetic testing to establish the condition.

Treatment

There is currently no cure for PROS, but treatments exist to manage symptoms and complications:

Surgical procedures: Surgeries may be performed to reduce overgrowth or relieve pain and other symptoms.
Medication: Research is ongoing into drugs that can inhibit the PIK3CA pathway, such as alpelisib, to reduce overgrowth.
Supportive care: Physical therapy, occupational therapy, and psychological support can help improve quality of life.

Living with PROS

PROS can have a significant impact on daily life. Regular medical monitoring is essential to address issues promptly. Families may benefit from working with specialized teams and connecting with patient organizations for support and information.

Summary

PROS is a rare, non-hereditary condition that causes excessive tissue growth due to a mutation in the PIK3CA gene. The condition is complex and varies greatly from person to person. While there is no cure yet, various treatments can help manage symptoms and improve quality of life.

Diseases related to PIK3CA gene mutations

PIK3CA gene mutations are associated with a variety of conditions that fall under the PIK3CA-Related Overgrowth Spectrum (PROS). These conditions are caused by somatic mutations in the PIK3CA gene and are characterized by abnormal tissue growth, often combined with other symptoms. Below are some conditions commonly associated with PROS, including their full names and abbreviations:

CLOVES Syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, and Skeletal/Scoliosis abnormalities): Congenital overgrowth of fatty tissue, vascular malformations, skin abnormalities, and skeletal issues.

MCAP Syndrome (Megalencephaly-Capillary Malformation Syndrome): Characterized by abnormally enlarged brains (megalencephaly), capillary malformations, and often neurological issues.

Klippel-Trénaunay Syndrome (KTS): Overgrowth of tissues and vascular abnormalities such as capillary, venous, and lymphatic malformations.

DCMO (Diffuse Capillary Malformation with Overgrowth): Diffuse capillary malformations combined with asymmetrical overgrowth.

FAVA (Fibroadipose Vascular Anomaly): A condition with fibroadipose overgrowth combined with vascular anomalies.

FIL (Facial Infiltrating Lipomatosis): Fatty tissue infiltrating facial structures, causing asymmetrical overgrowth.

HMEG (Hemimegalencephaly): Abnormal enlargement of one hemisphere of the brain, often associated with seizures and cognitive issues.

These conditions are rare and can present significant medical and psychological challenges. Genetic testing is often used to better understand and provide personalized treatment for these disorders.