Participants will receive oral sirolimus with a target blood concentration of 9-15ng/ml continuously for 12 months.

Participants will receive oral sirolimus with a target blood concentration of 3-7ng/ml continuously for 12 months

Participants will receive oral placebo(starch formulation) for 12 months.

Sirolimus is an mTORC1 inhibitor that has received approval from the U.S. Food and Drug Administration (FDA) and has recently been successfully used to treat lymphatic malformations and venous/lymphatic malformations associated with the same PIK3CA GOF mutations.

A serious adverse event is an SAE occurring during any study phase that fullfils one or more of the following criteria:

i. Results in death, ii. Is life-threatening, iii. Requires inpatient hospitalization or prolongation of existing hospitalization, iv. Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, v. Is an important medical event that may jeopardize the patient or may require medical intervention to prevent one of the outcomes listed above.

SAE will be assessed at each follow-up visit (15 days, 2 months, 6 months, 12 months, 18 months, 24 months). During the trial, participants can promptly report potential SAEs to the research team via the telephone. We will establish continuous, real-time communication with patients via the telephone, facilitating round-the-clock reporting of potential endpoints or adverse reactions to the clinical trial investigators.

Based on prior clinical experience and reports from sirolimus trials, adverse events (AE) have included oral ulcers, upper respiratory tract infections, headaches, respiratory illnesses, stomatitis, seizures, and fever. Other commonly reported AEs are nausea, vomiting, fatigue, dizziness, diarrhea, and mild allergic reactions such as rash or itching. Minor infections, mild gastrointestinal disturbances, and fluctuations in blood pressure or heart rate have also been observed.

Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or any life-threatening problem or death caused by or associated with sirolimus, if that effect, problem or death was not previously identified in nature, severity or degree of incidence in the investigational plan, or any other unanticipated serious problem associated with sirolimus that related to the rights, safety or welfare of subjects.