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Protocol Details

A Prospective Natural History Study of Lymphatic Anomalies

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 1 days
Max Age: 100 Years

Referral Letter Required


Population Exclusion(s)



Protein Losing Enteropathy;
Kaposiform Lymphangiomatosis;
Gorham Stout Disease;
Generalized Lymphatic Anomaly;
Complex Lymphatic Anomaly;
Chylous Effusion;
Chylous Ascites;
Central Conducting Lymphatic Anomaly

Recruitment Keyword(s)



Lymphatic Diseases;
Lymphatic Abnormalities

Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Institute of Child Health and Human Development


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.


To better understand why lymphatic anomalies develop. The goal is to improve future treatments.


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.


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.

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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


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.

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M(SqrRoot) kinen T, Boon LM, Vikkula M, Alitalo K. Lymphatic Malformations: Genetics, Mechanisms and Therapeutic Strategies. Circ Res. 2021 Jun 25;129(1):136-154. doi: 10.1161/CIRCRESAHA.121.318142. Epub 2021 Jun 24. PMID: 34166072.

Brouillard P, Witte MH, Erickson RP, Damstra RJ, Becker C, Qu(SqrRoot)(Copyright)r(SqrRoot)(Copyright) I, Vikkula M. Primary lymphoedema. Nat Rev Dis Primers. 2021 Oct 21;7(1):77. doi: 10.1038/s41572-021-00309-7. PMID: 34675250.

Liu M, Smith CL, Biko DM, Li D, Pinto E, O'Connor N, Skraban C, Zackai EH, Hakonarson H, Dori Y, Sheppard SE. Genetics etiologies and genotype phenotype correlations in a cohort of individuals with central conducting lymphatic anomaly. Eur J Hum Genet. 2022 Sep;30(9):1022-1028. doi: 10.1038/s41431-022-01123-9. Epub 2022 May 24. Erratum in: Eur J Hum Genet. 2022 Jun 3;: PMID: 35606495; PMCID: PMC9436962.

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Principal Investigator

Referral Contact

For more information:

Sarah E. Sheppard, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 2-5130
(240) 578-5047

Andrea I. Bowling, C.R.N.P.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 2-5152
(301) 451-3824

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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