CLOVES Syndrome

What is CLOVES?

Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevis, Spinal/Skeletal Anomalies/Scoliosis (CLOVES) syndrome is a very rare congenital (present at birth) disorder characterized by a combination of vascular (involving the blood vessels), skin, spinal, and bone or joint abnormalities.

Fewer than 200 cases of CLOVES syndrome have been identified worldwide to date. CLOVES is thought to be caused by mutations in a gene called PIK3CA. The long-term picture for a child with CLOVES depends on age and how serious the symptoms are. The sooner the disease is detected and the proper course of treatment is started, the better the general outlook.

What are the symptoms of CLOVES?

The symptoms of CLOVES can vary a great deal from child to child and can range from mild to severe. They are always present at birth but might not be noticeable right away, depending on how extensive they are.

Generally, in order to be diagnosed with CLOVES syndrome, a child will have one or more of the following:

  • soft, fatty masses on their torso or trunk (usually on their back, flank, or abdomen)
  • vascular (blood vessel) malformations — most often, a port wine stain birthmark, lymphatic malformation, arteriovenous malformation, or enlarged veins or a combination of these
  • limb abnormalities (typically, wide feet or toes and large or extra fingers or toes)
  • spinal problems (in many cases, scoliosis or tethered spinal cord). The presence of these abnormalities often indicates that a child is more likely to have CLOVES syndrome instead of a similar disorder.
  • skin abnormalities (most often, raised, wart-like bumps called epidermal nevi)

Less common symptoms can include:

  • problems with knee or hip joints
  • kidneys that are unusually small or uneven in size

What causes CLOVES syndrome?

Research by Matthew Warman, MD, director of Boston Children’s Orthopedic Research Laboratories, and pathologist Kyle Kurek, MD, has revealed that CLOVES is caused by mutations in a gene called PIK3CA. These mutations arise spontaneously in the womb, while a baby is developing. Thus far, there are no known risk factors that would make these mutations more or less likely to occur.

How we care for CLOVES syndrome

CLOVES was first described as a unique condition in 2009 by a clinical and research team led by Ahmad Alomari, MD, co-director of the Vascular Anomalies Center at Boston Children's. Our experience in treating numerous patients with CLOVES syndrome gives us the depth of knowledge about what symptoms to look for and how to plan treatment accordingly.

Our team takes an interdisciplinary approach to care with every child we see. That means that clinicians from many different specialties, all with expertise in treating CLOVES, will see your child as a team. This kind of approach is critical with CLOVES, as it can affect many different parts of a child's body.

Our areas of innovation for CLOVES syndrome

The VAC has generated an extensive case database on vascular anomalies, including CLOVES. Using this database, VAC clinicians conduct research that may lead to the development of new, more effective therapies and perhaps ultimately result in ways to prevent CLOVES and other vascular anomalies. As our database grows, it will help shine more light on CLOVES and other vascular anomalies.