Rare Medical News

Disease Profile

Milroy disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q82.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hereditary lymphedema; Congenital hereditary lymphedema; Early onset lymphedema;

Categories

Blood Diseases; Congenital and Genetic Diseases; Eye diseases;

Summary

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 buildup in the legs and feet and sometimes, within the body (nonimmune hydrops). After birth, symptoms may include swelling of the lower limbs, a buildup 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 the symptoms, a clinical exam and other types of testing. The diagnosis may be confirmed by genetic testing. Treatment is focused on managing the symptoms.

Symptoms

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]

  • Buildup of fluid (lymphedema) in the lower limbs
  • Fluid buildup 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]

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.

Medical Terms Other Names
Learn More:
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

Cause

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.

Diagnosis

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]

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

    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
    • Physician specializing in lymphedema
    • Vascular surgeon
    • Physical therapist
    • Dermatologist

    Organizations

    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

      Learn more

      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.

          References

          1. Brice GW, Mansour S, Ostergaard P, Connell F, Jeffery S, Mortimer P. Milroy Disease. GeneReviews. Updated September 25, 2014; https://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.

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