A Prospective Natural History Study of Lymphatic Anomalies

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.