What Is CLOVES Syndrome?

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CLOVES syndrome is an extremely rare congenital disease, which means that a person is born with the condition. It causes an overgrowth of fatty tissue lumps found under the skin and unusually formed blood vessels throughout the body.

People with CLOVES syndrome can also have spinal or skeletal issues. To date, fewer than 200 CLOVES cases have been officially reported worldwide.

CLOVES syndrome is named for the various issues that it causes:

  • Congenital (present from birth)
  • Lipomatous Overgrowth (fatty tissue lumps)
  • Vascular malformations (blood vessel abnormalities)
  • Epidermal nevi (skin lesions or moles)
  • Scoliosis or spinal deformities (curved spine or abnormally formed bones)
Treatment for CLOVES Syndrome

Verywell / Laura Porter

CLOVES Syndrome Symptoms

CLOVES syndrome affects the body’s tissue, blood vessels, bones, and some internal organs. Its symptoms are usually recognizable at birth or shortly after.

Some of the most common symptoms include:

  • Fatty tissue overgrowth: Soft lumps—also called lipomas—that form under the skin are often found on the stomach, back, and sides of CLOVES syndrome patients.
  • Blood vessel abnormalities: Veins—a type of blood vessel that carries blood back to the heart from various parts of the body—may be abnormally formed or larger than average. This can increase the risk of developing a blood clot.
  • Spinal problems: CLOVES syndrome may cause a curvature of the spine (known as scoliosis) or a tethered spinal cord, which is when the spinal cord becomes problematically attached to the tissue around the spine.
  • Asymmetric body parts: One side of the face, head, arms, or legs may be visibly shaped and sized differently than the other side. This includes large or wide hands and feet, along with unusual spacing between the fingers and toes. 
  • Skin lesions: Unusually colored patches, birthmarks, or moles (also called nevi) are often found on the skin.
  • Kidney abnormalities: CLOVES syndrome can cause issues with the kidneys, such as having one kidney that’s larger than the other, or only having one kidney.
  • Intestinal and bladder issues: Some patients may experience bleeding from the intestines (a part of the digestive system) or the bladder (responsible for collecting and getting rid of the body’s urine).

Not everyone with CLOVES syndrome will experience all of these symptoms, but rather some combination of them. In addition, CLOVES syndrome symptoms can vary from mild to severe.


CLOVES syndrome is caused by a gene mutation (a change) that is thought to happen during the baby’s early development in the womb. Genes are responsible for determining a person’s features or traits.

In CLOVES syndrome, a change happens in the gene known as PIK3CA. It is a growth regulatory gene, meaning it plays an important role in instructing the body’s cells to grow or divide. When there is a mutation in the PIK3CA gene, cells can grow uncontrollably—leading to the overgrowth of fatty tumors and other issues.

Even though it’s related to a gene mutation, CLOVES syndrome is a nonhereditary disorder, meaning that it is not passed down from parent to child. In the case of CLOVES, the PIK3CA gene mutates on its own, with no known reason. Experts call this a sporadic mutation.


To diagnose CLOVES syndrome, a doctor will start by looking for its signature combination of skin, blood vessel, and spinal problems. This can be done through a physical exam.

From there, a suspected CLOVES syndrome diagnosis can be confirmed through the following methods:

  • Imaging: X-ray or magnetic resonance imaging (MRI) gives the doctor an inside view of any tissue or bone abnormalities in the chest, stomach, pelvis, spine, and limbs.
  • Ultrasound: High-frequency sound waves are used to look at the organs in the abdomen, such as the kidneys. It can detect size or shape changes in organs, tissues, and blood vessels, and may show if there’s a tumor mass present. Ultrasound can also be used to check for CLOVES syndrome prenatally (while the baby’s still in the womb).
  • Genetic testing: Also known as a DNA test, sometimes a blood test can be used to confirm a mutation of the PIK3CA gene that causes CLOVES syndrome. This test is not always used, though, because experts have found that it isn’t always accurate. A DNA test is not required to form a CLOVES syndrome diagnosis.

Of note, patients with CLOVES syndrome are at times misdiagnosed as having Klippel-Trenaunay syndrome or Proteus syndrome, since the syndromes have very similar symptoms.

Similar Conditions

CLOVES syndrome is part of a group of similar conditions that also cause tissue overgrowth and blood vessel abnormalities. This group is referred to as PIK3CA-related overgrowth spectrum, or PROs.


There is currently no cure for CLOVES syndrome, but a team of doctors can help treat and manage the various symptoms that it causes.

Depending on the specific case, this medical team can include a general surgeon, geneticist, radiologist (a doctor who specializes in imaging like X-rays), hematologist (a doctor who specializes in blood disorders), and orthopedist (a doctor who specializes in correcting bone abnormalities), among others.

Treatment plans will vary by person, but they can commonly include:

  • Medication: An immune system medication taken by mouth called sirolimus can help control some of the blood vessel abnormalities, such as infections, bleeding, and enlarged masses of blood vessels.
  • Sclerotherapy and embolization: These minimally invasive procedures help shrink enlarged blood vessels and block the flow of blood to a fatty tumor.
  • Debulking surgery and general surgery: Surgery is often used to remove fatty tissue overgrowths, which helps with body function and visible abnormalities.
  • Orthopedic procedures: Surgeries done on the bones can help correct any limb or joint abnormalities. 
  • Neurosurgery: Surgery can help repair a tethered spinal cord or a tissue mass that has formed on or around the spine. 
  • Rehabilitation therapies: Physical and occupational therapy are often treatment options for patients who have undergone surgeries or procedures. 
  • Regular ultrasound screening: Starting at age 8, experts recommend kidney screening to check for Wilms tumor, a childhood cancer that affects the kidneys.

Ongoing Care

In addition to getting specific treatments, it is recommended that CLOVES syndrome patients follow-up with their medical team very regularly throughout childhood. This way, doctors can keep checking for any new skin overgrowths or other complications.


Each case of CLOVES syndrome is different, so outcomes will vary in part based on how old the child is when diagnosed and how serious the symptoms are.

One thing that all CLOVES syndrome cases have in common is the importance of getting diagnosed as early as possible. The sooner that CLOVES can be diagnosed, evaluated, and treated, the better the general outcome is for the patient’s overall health and quality of life.


CLOVES syndrome is a rare condition that a person is born with. It causes issues with skin overgrowths, blood vessels, and the spine. The underlying cause is a gene mutation that is not inherited.

It is diagnosed by physical examination and imaging. Treatment depends on the symptoms the person has, which vary from case to case and may include medication, surgery, and therapies.

A Word From Verywell

CLOVES syndrome is not only very rare, but it’s also very new for scientists and researchers, who are studying this condition and potential new treatments. There are still many unknowns about CLOVES syndrome and the complications it causes.

Experts are encouraged by the fact that many children with CLOVES can live healthy, normal lives with routine medical care, particularly when the condition is on the mild side and diagnosed early on.

Your child’s medical team will be able to give you more specifics about the recommended care plan and long-term health outlook. In the meantime, know that you are not alone. Support is available for families experiencing a CLOVES syndrome diagnosis through organizations like CLOVES Syndrome Community and Understanding PROS.

Frequently Asked Questions

How many children have CLOVES syndrome?

CLOVES syndrome is very rare. Fewer than 200 cases have been reported worldwide. Based on that data, researchers think that CLOVES affects males and females of all ages, races, and ethnicities equally.

How do doctors test for CLOVES syndrome before birth?

Doctors can sometimes detect blood vessel overgrowth, fatty tissue, and spinal issues through an ultrasound while the baby is still in the womb. Otherwise, CLOVES syndrome can be diagnosed at birth.

What does CLOVES syndrome treatment involve?

Treatment will vary based on the specific symptoms. Some common options include: oral medication for blood vessel abnormalities, surgery to remove fatty tissue overgrowths, and orthopedic support for issues with the bones.

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11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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