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

CLOVES syndrome


Other Names:
Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities; Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi; CLOVE syndrome; Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities; Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi; CLOVE syndrome; Congenital lipomatous overgrowth - vascular malformation - epidermal nevi See More
Categories:
This disease is grouped under:
CLOVES syndrome is a rare condition that is primarily characterized by congenital overgrowth of fatty tissue; malformations of the vascular system (the vessels that carry blood and lymph throughout the body); epidermal nevi; and spinal or skeletal abnormalities. Other signs and symptoms may include disproportionate fat distribution, overgrowth of the extremities (arms and legs), skin abnormalities and kidney problems such as an unusually small or absent kidney.[1][2][3] The severity of the condition and the associated signs and symptoms vary significantly from person to person. CLOVES syndrome is caused by somatic mutations in the PIK3CA gene.[2][4] Because these mutations do not affect egg or sperm cells, the condition is not passed on from parent to child. Treatment is based on the signs and symptoms present in each person.[2][3]
Last updated: 10/5/2016

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
Learn More:
HPO ID
100% of people have these symptoms
Hemihypertrophy
Asymmetric overgrowth
0001528
30%-79% of people have these symptoms
Lipoma
Fatty lump
Noncancerous fatty lump
[ more ] 		0012032
5%-29% of people have these symptoms
Lower limb asymmetry
Left and right leg differ in length or width
0100559
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney
[ more ] 		0008678
Scoliosis 0002650
Spinal dysraphism 0010301
Tethered cord 0002144
Percent of people who have these symptoms is not available through HPO
Capillary malformation 0025104
Cranial hyperostosis 0004437
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face
[ more ] 		0000324
Macrodactyly
Finger overgrowth
0004099
Overgrowth
General overgrowth
0001548
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe
[ more ] 		0001852
Splenomegaly
Increased spleen size
0001744
Sporadic
No previous family history
0003745
Venous malformation 0012721
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Last updated: 7/1/2020
Treatment for CLOVES syndrome involves addressing each symptom or complication and improving quality of life (palliative care).[5] There is currently no cure. Palliative care aims to relieve symptoms caused by masses and minimize disease progression and disability. Management is very individualized because symptoms can vary in severity and body location for each person. Follow-up with various specialists is recommended every 6 months until the end of puberty, to assess for overgrowth and complications.[2]

Medical treatment may include embolization and surgical removal of masses, especially those that are large, deep, or in the spinal region.[2] Sclerotherapy may be used in adults to lessen pain and reduce the size of vascular and lymphatic malformations.[2]

Orthopedic and neurosurgical checkups with possible surgical intervention are needed to reduce complications from overgrowth. Surveillance of hands, feet, and limb abnormalities is important so surgery can be done promptly to minimize limb disfigurement and loss of function. Because there is increased risk of tumor growth in people with overgrowth syndromes, people with CLOVES syndrome should have surveillance for tumors and have masses assessed.[2]

In general, the earlier surveillance and intervention are started, the better the outcome.[2]
Last updated: 5/9/2017

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 CLOVES syndrome. 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.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with CLOVES syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for CLOVES syndrome:
    CLOVES Contact 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.

In-Depth Information

  • 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 CLOVES syndrome. 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.

  1. CLOVES Syndrome Factsheet. CLOVES Syndrome Community. August 2011; http://www.clovessyndrome.org/sites/default/files/CSC_onepager.pdf.
  2. Anderson S, Brooks SS. An Extremely Rare Disorder of Somatic Mosaicism: CLOVES Syndrome. Adv Neonatal Care. October 2016; 16(5):347-359.
  3. Martinez-Lopez A, Blasco-Morente G, Perez-Lopez I, Herrera-Garcia JD, Luque-Valenzuela M, Sanchez-Cano D, Lopez-Gutierrez JC, Ruiz-Villaverde R, Tercedor-Sanchez J. CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS). Clin Genet. July 2016; [epub ahead of print]:
  4. Congenital Lipomatous Overgrowth, Vascular Malformation, and Epidermal Nevi. OMIM. 8/2013; http://www.omim.org/entry/612918.
  5. Frequently Asked Questions -- Compiled from doctors, families, and people with CLOVES. CLOVES Syndrome Community. February 2017; http://www.clovessyndrome.org/content/faqs.