A Prospective Natural History Study of Lymphatic Anomalies

Background: The lymphatic system is a network of vessels that carry a clear fluid called lymph through the body. Problems in the lymphatic system can cause pain, fluid buildup, and issues with immunity. There is much researchers do not understand about lymphatic anomalies. In this natural history study, they will collect data from a lot of people over a long time. Objective: To better understand why lymphatic anomalies develop. The goal is to improve future treatments. Eligibility: People aged 0 days and older with a suspected or confirmed lymphatic anomaly. Their unaffected parents or siblings aged 7 years or older are also needed. Design: Participants may remain in the study indefinitely. Affected participants may be evaluated every 10 months to 2 years. Some participants will be seen over telemedicine. Others will be seen at the NIH Clinical Center for 2-5 days. All participants will have a physical exam. They may provide specimens including blood, saliva, hair follicles, stool, skin, and other tissues. Samples may be used for genetic testing. Participants may undergo other tests depending on their medical conditions. The NIH Clinical Center visit may include: Heart tests include placing stickers on the chest to measure electrical activity and using sound waves to capture pictures of the heart. A lung test measures the muscle strength in the chest. Participants will blow into a tube. Photographs may be taken of participants faces and other features. Imaging scans will take pictures of the inside of the body. One scan will measure bone density. One type of scan tracks how lymph fluid moves through the body. Participants will be under anesthesia, and they will be injected with a dye.

Study Description: A natural history study for lymphatic anomalies to systematically evaluate the disease phenotypes and long-term outcomes to provide improved prognostication to families, establish screening/monitoring guidelines, determine best practices for genetic diagnosis, explore family opinions, and explore fertility for those on long term medication management. This study will allow us to identify novel end points for future clinical trials. Objectives: Primary objectives: * To establish a longitudinal cohort of participants with lymphatic anomalies * To longitudinally determine the age at presentation and incidence of clinical features Secondary objectives: * To establish a longitudinal biospecimen repository * To determine the best practices for genetic diagnosis based on phenotype. * To determine the malignant potential of anomalies longitudinally Endpoints: Primary endpoints: * The number of participants with lymphatic anomalies * For each clinical feature or symptoms, the range of ages at the development of that feature/symptom and fraction of participants with that feature * Quantification and identification of novel features associated with disease. Secondary endpoints: * The number of specimens collected * Diagnostic yields by phenotype and genetic test methodology * Number of malignancies related to the primary lesion that have developed

* INCLUSION CRITERIA: Affected (Proband) In order to be eligible to participate in this study, an individual must meet one of the following criteria as determined after review of medical history: * Current or history of lymphatic anomaly or symptoms suggestive of a lymphatic disorder Or * An ill-defined vascular anomaly that is suspected to have an abnormal lymphatic component Or * A pathogenic, likely pathogenic, or VUS in a genetic disorder with a known lymphatic component Or * Clinical diagnosis of a syndrome with a known lymphatic component Unaffected (First Degree Relatives: Parents and Siblings) Genetic variants underlying complex lymphatic anomalies can be passed down through parents or be new in a child (de novo). Inclusion of first-degree relatives will assist in genetic analysis to delineate whether the variant is inherited or de novo. To be eligible to participate as a first degree relative in this study, an individual must be a first-degree family member of an affected participants EXCLUSION CRITERIA: Affected Proband An individual who meets any of the following criteria will be excluded from participation in this study after review of medical history, concomitant medication and allergy review, anthropometrics, and performance status: -Any condition, in the opinion of the investigator, that would increase risk of participation or impair their ability to comply with protocol requirements. Lymphatic anomalies that are definitively determined to be secondary by the principal investigator will be excluded from this study. For example, participants who develop a lymphedema after breast cancer surgery. Unaffected (First Degree Relatives) -Any condition, in the opinion of the investigator, that would increase risk of participation or impair their ability to comply with protocol requirements.