National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Milroy disease


Other Names:
Hereditary lymphedema; Congenital hereditary lymphedema; Early onset lymphedema; Hereditary lymphedema; Congenital hereditary lymphedema; Early onset lymphedema; Hereditary lymphedema 1; Primary congenital lymphedema; Nonne-Milroy syndrome; Nonne-Milroy disease; Milroy's disease; Nonne’s syndrome; Congenital primary lymphedema; Hereditary lymphedema type I; Nonne-Milroy lymphedema See More
Categories:
Milroy disease affects the lymphatic system and can lead to swelling (lymphedema) of the legs and feet. Prior to birth, symptoms of Milroy disease may include fluid build up in the legs and feet and sometimes, within the body (nonimmune hydrops). After birth, symptoms may include swelling of the lower limbs, a build-up of fluid in the scrotum (hydrocele), and skin changes. People with Milroy disease have an increased risk for developing skin infections and certain types of cancer. Milroy disease occurs when the FLT4 gene is not working correctly. It is inherited in an autosomal dominant pattern. The diagnosis of Milroy disease is made based on a medical exam, other types of testing, and may be confirmed by genetic testing. Treatment is focused on managing the symptoms.

Last updated: 7/7/2020
The following list includes the most common signs and symptoms in people with Milroy disease. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[1]
  • Build-up of fluid (lymphedema) in the lower limbs
  • Fluid build up in the scrotum (hydrocele)
  • Easily seen veins
  • Upslanting toenails
  • Wart-like growths (papillomatosis)
  • Skin infection (cellulitis)
Swelling of the lower limbs is usually present from before birth. It may gets worse over time, but in some cases lymphedema may improve. Skin changes may develop over the area of lymphedema, including thickened, scaly skin (hyperkeratosis) and wart-like growths (papillomatosis). People with Milroy disease may have an increased risk for developing serious skin infections and cancer.[2][3]
Last updated: 7/7/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
30%-79% of people have these symptoms
Ankle swelling 0001785
Cellulitis
Bacterial infection of skin
Skin infection
[ more ] 		0100658
Hydrocele testis 0000034
Hyperkeratosis 0000962
Pedal edema
Fluid accumulation in lower limbs
Lower leg swelling
[ more ] 		0010741
Predominantly lower limb lymphedema 0003550
Toenail dysplasia
Abnormal toenail development
0100797
Varicose veins 0002619
5%-29% of people have these symptoms
Angiosarcoma 0200058
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Lichenification 0100725
Neoplasm of the skin
Skin tumors
Tumor of the skin
[ more ] 		0008069
Specific learning disability 0001328
1%-4% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Erysipelas 0001055
Hypoplasia of lymphatic vessels
Underdeveloped lymphatic vessels
0003759
Nonimmune hydrops fetalis 0001790
Papilloma 0012740
Prominent superficial veins
Prominent veins
0001015
Upslanting toenail 0032344
Urethral stricture 0012227
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Congenital onset
Symptoms present at birth
0003577
Hemangioma
Strawberry mark
0001028
Hyperkeratosis over edematous areas 0007448
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Last updated: 7/1/2020
Milroy disease occurs when the FLT4 gene is not working correctly.[1][4] DNA changes known as pathogenic variants are responsible for affecting how genes work.
Last updated: 7/7/2020
Milroy disease is inherited in an autosomal dominant pattern.[8196] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent.  Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family.
  
Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.  

Last updated: 7/7/2020
Milroy disease is diagnosed based on symptoms and clinical exam findings. Lymphoscintigraphy, a test done to check the lymphatic system for disease, can also be performed to help with the diagnosis. The diagnosis may be confirmed by molecular genetic testing of the FLT4 gene.[1][2]
Last updated: 7/7/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment of Milroy disease is focused on managing the symptoms. The lymphedema of the legs and feet may be controlled with the help of a lymphedema therapist, massage, compression stockings, or bandaging. If this management is ineffective then surgical treatment may be considered.[1][5][6]

Specialists who may be involved in the care of someone with Milroy disease include:
  • Lymphedema therapist
  • Physical therapist
  • Dermatologist
Last updated: 7/7/2020
The number of people with Milroy disease is not known. About 200 cases have been reported in the literature. Milroy disease is occurs in all ethnic groups, and usually affects females more than males.[1][5]
Last updated: 7/7/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Milroy disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Milroy disease. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Milroy disease. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Are there any clinical trials or testing being done anywhere on Nonne-Milroy disease? See answer


  1. Brice GW, Mansour S, Ostergaard P, Connell F, Jeffery S, Mortimer P. Milroy Disease. GeneReviews. Updated September 25, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1239/.
  2. Connell FC, Ostergaard P, Carver C, Brice G, Williams N, Mansour S, Mortimer PS, Jeffery S. Lymphoedema Consortium. Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. Hum Genet. Jan 2009; 124(6):625-31. https://pubmed.ncbi.nlm.nih.gov/19002718.
  3. Arriola AG, Taylor LA, Asemota E, Boos MD, Elder DE, Weber KL, Micheletti RG, Zhang PJ. Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature. J Cutan Pathol. Jan 2017; 44(1):98-103. https://pubmed.ncbi.nlm.nih.gov/27730656.
  4. DiGiovanni RM, Erickson RP, Ohlson EC, Bernas M, Witte MH. A novel FLT4 mutation identified in a patient with Milroy disease. Lymphology. Mar 2014; 47(1):44-7. https://pubmed.ncbi.nlm.nih.gov/25109169.
  5. Hereditary Lymphedema. National Organization for Rare Disorders (NORD). Updated 2015; https://rarediseases.org/rare-diseases/hereditary-lymphedema.
  6. Bolletta A, Di Taranto G, Chen SH, Elia R, Amorosi V, Chan JC, Chen HC. Surgical treatment of Milroy disease. J Surg Oncol. 2020; 121(1):175-181. https://pubmed.ncbi.nlm.nih.gov/31165487.
  7. Boudon E, Levy Y, Abossolo T, Cartault F, Brouillard P, Vikkula M, Kieffer-Traversier M Ramful D, Alessandri JL.. Antenatal presentation of hereditary lymphedema type I. Eur J Med Genet. Jun-Jul 2015; 58(6-7):329-31. https://pubmed.ncbi.nlm.nih.gov/25896638.