A Prospective Natural History Study of Lymphatic Anomalies

Study Overview
=================
Brief Summary
-----------------
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. Visits may take up to 8 hours, over 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: A 6-minute walk test measures physical function. 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.

Detailed Description
-----------------
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

Official Title
-----------------
A Prospective Natural History Study of Lymphatic Anomalies

Conditions
-----------------
Lymphatic Diseases, Lymphatic Abnormalities

Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| First Degree Relatives<br>Siblings or parents of patients. | |
| Patients<br>Patients with lymphatic anomalies. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish a longitudinal cohort of participants with lymphatic anomalies | We plan to enroll a group of participants willing to participate in the study over time. | 12/31/2028 | 
| To longitudinally determine the age at presentation and incidence of clinical features | For each clinical feature or symptoms, the range of ages at the development of that feature/symptom and fraction of participants with that feature | 12/31/2028 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish a longitudinal biospecimen repository | We plan to collect biospecimens including, but not limited to blood and stool from participants over time. | 12/31/2028 | 
| To determine the best practices for genetic diagnosis based on phenotype | We will analyze diagnostic yields by phenotype (how many participants are able to have a genetic diagnosis in proportion to the number of participants who receive genetic testing) and genetic test methodology (to determine which genetic test is most helpful in diagnosing lymphatic anomalies) | 12/31/2028 | 
| To determine the malignant potential of anomalies longitudinally | We will track the number of malignancies related to the primary lesion that have developed | 12/31/2028 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Protein Losing Enteropathy, Lymphedema, Lymphangiectasia, Kaposiform Lymphangiomatosis, Gorham Stout Disease, Generalized Lymphatic Anomaly, Complex Lymphatic Anomaly, Chylous Effusion, Chylous Ascites, Central Conducting Lymphatic Anomaly