PIK3CA-Related Overgrowth Spectrum, commonly referred to as PROS, is a term that encompasses a diverse group of rare syndromes. These syndromes share a common characteristic: they involve abnormal growth or the development of unusual shapes in various parts of the body. These manifestations result from genetic alterations, known as mutations, in a gene called PIK3CA.
PROS presents a unique challenge due to the wide array of body parts it can affect. This condition can result in excessive growth or atypical development in the skin, blood vessels, bones, fat tissues, and even the brain. The symptoms of PROS can vary significantly, depending on the specific type of syndrome within the spectrum and which areas of the body are impacted. In some cases, these symptoms are visible at birth, allowing for an immediate diagnosis, while in others, the condition may become apparent later in childhood.
Unpacking PIK3CA and PROS
PROS arises from changes in the PIK3CA gene. To comprehend how these genetic alterations lead to PROS, it is essential to understand the gene’s role in the human body. Like many genes, PIK3CA contains instructions for synthesizing a specific protein. The PIK3CA protein plays a pivotal role in regulating other proteins that act as vital signaling molecules in the body. These signals are responsible for ensuring that cells grow, divide, move, and undergo programmed cell death when necessary.
When cells do not receive the correct instructions from PIK3CA, the protein cannot fulfill its role effectively. Faulty PIK3CA leads to errors in cell growth. When these errors cause cells to proliferate and divide too rapidly or survive beyond their normal lifespan, it results in overgrowth or the development of unusual shapes in the affected body parts.
In individuals with PROS, abnormal growth can be localized to specific areas of the body rather than affecting all tissues. This is because the mutations responsible for PROS generally occur in only some of an individual’s cells.
Remarkably, unlike many other genetic conditions, PROS is not hereditary. Consequently, if a child is diagnosed with PROS, it does not imply that their parents have the condition or that their other children will be affected.
Diverse Types of PROS
The term “PROS” is an umbrella that encompasses several distinct syndromes, each with its own unique characteristics. While some individuals receive a direct PROS diagnosis, others may be diagnosed with one of the specific syndromes falling under the PROS spectrum. Notable syndromes within PROS include:
1. Fibroadipose Hyperplasia: This form of PROS leads to localized growths on limbs or other areas of the body. These growths manifest when fatty or fibrous tissues, or blood vessels, experience excessive development. Over time, these growths tend to worsen and may interfere with mobility and other physical activities.
2. CLOVES Syndrome: The name of this condition is an acronym reflecting its defining features. “C” stands for congenital, signifying that it is present at birth. “L” is for lipomatous, referring to its association with fatty tissue, often manifesting as a visible fatty mass. “O” denotes overgrowth, while “V” points to vascular malformations, which can result in characteristics such as birthmarks or prominent veins. “E” signifies epidermal nevi, a type of skin lesion, while “S” includes spinal or skeletal issues, such as scoliosis. People with CLOVES may also exhibit additional signs, such as enlarged hands, feet, fingers, toes, and wide spaces between their digits.
3. Megalencephaly-Capillary Malformation (MCAP) Syndrome: MCAP syndrome within PROS leads to the overgrowth of the brain and various other body parts, including blood vessels and aspects of the face. Individuals with MCAP syndrome may experience developmental delays and exhibit unusual fingers and toes.
4. Hemihyperplasia-Multiple Lipomatosis (HHML) Syndrome: This type primarily affects the growth of arms and legs. HHML syndrome results in the gradual development of painless fatty masses beneath the skin in various parts of the body, with common locations being the back, torso, legs, arms, and fingers. Unusual blood vessels may also be present.
5. Hemimegalencephaly: In this PROS subtype, all or half of the brain exhibits abnormal enlargement. Additionally, changes in blood vessels may occur. Children with hemimegalencephaly may experience seizures, paralysis, and developmental delays.
6. Facial Infiltrating Lipomatosis: This disorder involves painless swelling or overgrowth of a section of the face, typically occurring on one side of the head. In some cases, masses develop from nerves, and parts of the tongue may exhibit abnormal enlargement. Bones and teeth can also be affected.
Managing PROS
While there is no cure for PROS, several strategies can be employed to manage the condition and its associated symptoms. Medical professionals may recommend surgical interventions to remove overgrowths, particularly when they hinder movement or daily activities. Surgery can also alleviate brain pressure, correct spinal deformities like scoliosis, or address other health concerns. Medications may be prescribed to mitigate symptoms like seizures or other manifestations.
The Path Ahead for Affected Children
PROS is a lifelong condition that can influence various aspects of a child’s daily life. Given the diversity of PROS and its capacity to affect different body parts, the prognosis and symptomatology can vary significantly from one person to another. For instance, when the brain is impacted, developmental delays and learning differences may arise.
Moreover, individuals with PROS may have an increased susceptibility to certain cancers. This connection between PROS and cancer is further underscored by the presence of PIK3CA gene alterations in some tumors of individuals with cancer who do not have PROS. Parents are encouraged to engage in discussions with healthcare providers to gain a clearer understanding of their child’s current and future cancer risk.
In conclusion, PIK3CA-Related Overgrowth Spectrum (PROS) presents a complex and multifaceted challenge, affecting various parts of the body. The unique nature of PROS necessitates tailored diagnostic approaches and a comprehensive understanding of the different syndromes that comprise this spectrum. Through diligent management and ongoing medical care, individuals with PROS can enhance their quality of life and well-being, navigating the intricacies of this condition.