Frequently Asked Questions – Compiled from doctors, families and people with CLOVES (Updated February 2017)
Is there a cure for CLOVES?
“Although there is no cure for CLOVES Syndrome, we can successfully address its complications. Our goal is to create a better quality of life for these children.” - Ahmad Alomari, MD Co-Director of the Children’s Hospital Boston Vascular Anomalies Center
Surgery and other medical interventions are the only treatments for CLOVES overgrowth, vascular anomalies and other related medical issues. Boston Children's Hospital started doing research into CLOVES via genome sequencing in March of 2011. This sequencing led to the PIK3CA genetic mutation discovery of CLOVES in May of 2012. If you are interested in learning more about this research opportunity, you can email Dr. Matthew Warman at Matthew.Warman@childrens.harvard.edu. In 2017, PIK3CA genetic testing is also available clinically (not just for research), though testing should be done on abnormal tissues after biopsy or resection and insurance approval should be cleared before committing to genetic testing.
In addition the National Institutes of Health (NIH) have recently expanded their eligibility criteria to include CLOVES Syndrome and related conditions. People with these conditions may be eligible to join this study. To find out more about the NIH research opportunity, please call (301) 435-6689. You can learn more about all research options for people with CLOVES on the website.
Are there any medicines to treat CLOVES?
As of January 2017, there is no open study of a medication to treat CLOVES. There is growing experience using sirolimus to manage some symptoms and complications of CLOVES, based on studies done by Drs. Denise Adams and Cameron Trenor at Boston Children’s Hospital. Sirolimus has been most effective at controlling infections, leaking from lymphatic vesicles, bleeding and enlarging vascular masses. The decision to recommend sirolimus is based on an individual patient’s complications and should be considered with your physician.
There are a few companies developing drugs for other reasons that happen to target this PIK3CA pathway. In the near future, these may be considered for patients with CLOVES in a clinical trial. We are happy to share contact information of experienced physicians with you, if you need it.
My child just got diagnosed with CLOVES Syndrome. A lot of what I have read is really scary. What can I expect for him in his lifetime?
As CLOVES is rare and was only defined in 2007, there are many unknowns still.
A new diagnosis of a rare syndrome like CLOVES can be a challenging time that may cause anxiety and stress for patients and families. We believe that connecting to others is an important component of a new diagnosis, and may help to put some of the uncertainty and concern into perspective. You can connect with other families in our secret, non-searchable Facebook group by "friending" our Welcome Account.
In addition, Boston Children’s Hospital, in collaboration with other centers, has a robust initiative to collect information from people currently diagnosed with CLOVES, in order to learn more about what the future holds for our loved ones. This project is called the Lymphatic Anomalies Registry.
CLOVES Syndrome Community maintains a Contact Registry. The CSC Registry will be used to inform individuals with CLOVES Syndrome and their guardians about:
- discoveries about CLOVES Syndrome that may impact care decisions
- opportunities to participate in research
- opportunities to contribute data
We encourage new members to sign up for our contact registry.
My child was diagnosed with Klippel-Trenaunay Syndrome (KTS) or Proteus Syndrome and now the doctors say s/he has CLOVES? What's the difference?
CLOVES is a relatively new diagnosis just identified in 2007. Anyone who was diagnosed before 2007, was diagnosed with a different syndrome, as CLOVES did not yet exist. All three syndromes listed above are similar because they encompass both vascular anomalies and overgrowth. Also confusing, Klippel-Trenaunay is caused by the same PIK3CA mutations that cause CLOVES. For this reason, some believe these diagnoses should lumped together into one disease and have proposed the name “PIK3CA-Related Overgrowth Syndromes (PROS).” One reason not to lump these together is that patients with CLOVES have risks of paraspinal and spinal complications and a kidney tumor called Wilms, while patients with Klippel-Trenaunay have not been shown to have these complications.
Additionally, people with CLOVES are born with some collection of physical differences and/or physical differences have been noted on prenatal ultrasound before birth. Conversely, people with Proteus syndrome are born without obvious physical differences, then they develop progressive overgrowth and skeletal concerns as the child gets older.
I’ve heard about a risk of blood clots related to CLOVES – what do I need to know?
Blood clots are more likely to occur in patients with CLOVES. While this has occurred at any age, most events happen after age 10 and the risk is higher around procedures. The main predictor of blood clot risk seems to be enlarged draining veins that occur in many patients with CLOVES. Before any major surgery, evaluation of enlarged veins to consider closing them and consultation with a hematologist for anticoagulation recommendations is recommended.
I also have concerns about the risk of Wilms tumor in CLOVES.
There have been four cases of Wilms tumor identified in patients with CLOVES syndrome. This is a rare complication of CLOVES, but the team at Boston Children’s Hospital has recommended screening kidney ultrasounds every 3 months until a child’s eighth birthday. This is similar to Wilms tumor screening in other overgrowth disorders. Wilms tumor is a very treatable kidney cancer. Screening with ultrasound is recommended because treatment is easier and chance of cure is very high when Wilms tumor is caught early. It is not clear why patients with CLOVES are more likely to develop this tumor.
My child's doctors don’t know much about CLOVES - what should I do?
The medical management of CLOVES is extraordinarily challenging, and we recommend that you consult a Multidisciplinary Vascular Anomalies Center that has expertise with both overgrowth and complex vascular anomalies. We can help you in finding a facility near you and/or a multidisciplinary practice to collaborate with you and your child's local physicians. We suggest that you read and print out the comprehensive screening guidelines for CLOVES and share them with your specialists.
Additionally, Boston Children’s Hospital has a process where they review your child’s medical records, and may be able to provide a diagnosis and treatment recommendations, sometimes without a visit to Boston. Call the Children’s Hospital Boston Vascular Anomalies Center at 617-355-5226 to find out more about the VAC Conference process. We also recommend participation in the Lymphatic Anomalies Registry (www.lymphaticregistry.org), which is coordinated at Boston Children’s Hospital and includes patients with CLOVES.
The NIH also has a similar research study whose goal is to better understand many different kind of overgrowth syndromes, including CLOVES syndrome. Participants in this study may also be invited to visit the NIH for an in-person evaluation or can send in a sample for genetic testing. You can call the NIH Overgrowth Study at 301-435-6689 to find out more about this study. If you want to share some information about CLOVES syndrome with your doctors, you can give them this paper which describes 35 different patients with CLOVES syndrome.
Is tethered cord something you are born with or can it develop later in life?
Tethered cord means that the spinal cord has some kind of attachment that prevents the spinal cord from moving freely within the spinal canal. This attachment is usually some type of tissue that children have from birth, like a fatty filum (strand of fat), lipoma (bigger collection of adipose - fat - tissue) or dermal sinus tract (strand of tissue from outside the spinal canal to the spinal cord). However, sometimes tethering can occur later in life, especially after surgery (when scar tissue can stick the spinal cord to the lining of the spinal canal) or after a bad infection, like meningitis (when the inflammation of the infection can lead to scar tissue). It is important to understand that there is a difference between radiographic tethering (which means that the MRI or other imaging studies show some kind of connection, but which may NOT have symptoms and may NOT need surgery) and clinical tethering (which means that one sees a site of tethering on imaging AND there are symptoms that can be directly related to the things that are seen on the imaging). If there is an attachment that is thought to be tugging on the spinal cord, then sometimes symptoms can develop - depending on where the tethering occurs - that can lead to problems with spinal cord function (like weakness, sensory changes, scoliosis (bend in the back) or pain). The diagnosis of tethered cord can be difficult and it is important to talk with physicians who see these conditions routinely in order to put together the best plan of treatment for your child.
What are the reasons for not surgically treating tethered cord?
As mentioned above, there may be situations in which one can see some kind of tethering (attachment from scar tissue or birth-related structures) on imaging studies (like MRI), but which are not causing any symptoms. In some cases, it may be that the risk of doing surgery to disconnect the tethering site may be greater than the risk of leaving things alone. On the other hand, there are sometimes situations when the child has no symptoms, but the imaging shows a problem that will very likely become worse with time, in which case the risk of surgery - even with no symptoms - may be justified. If a patient is fully grown and has not developed symptoms, the chances of future problems from tethering become very small. The decision to operate or to monitor a tethered cord is often very dependent on individual MRI findings, symptoms and co-exisiting medical conditions, so it is important to talk to your doctor to learn about the pros and cons of different management plans.
Why do some people with CLOVES have scoliosis?
For now, this is an unexplained association with CLOVES. Asymmetric growth of one side faster than the other may be one theory. This is important to follow over time in CLOVES patients, especially before pubertal growth, so that any possible interventions to straighten the spine be employed during growth and before surgical rod placement is necessary.
My child just got a new lump on their body. What am I supposed to do?
New lumps and bumps can cause concern in CLOVES. Gradually enlarging lumps that feel like fatty tissue may be just that – lipomas. Rapidly expanding bumps may be infected (red, painful, fever) or newly blood-filled (purple, painful) lymphatic cysts or clotted venous malformations (painful, bruise-colored, hard). Physician evaluation is recommended for slow-growing hard lesions, lesions unlike others you’ve seen before in CLOVES, or for any lesions causing concern or needing medication (pain med, antibiotic) to speed recovery.
My child’s doctors are suggesting that my child have a large vein removed. I don’t understand why.
Many people with CLOVES are born with a large vein or veins. The concern about large veins and CLOVES is that the blood becomes stagnant (slow moving) and when the blood is not flowing effectively, there is an increased risk of a clot or multiple clots (also called a deep vein thrombosis, or DVT). The decision to remove or close a large vein should be directed by an expert in this procedure, and by weighing risks and benefits of removal. Options for treatment are by surgery, radio ablation (laser from inside the vein) or the vein may need be carefully monitored or observed. Removing a vein that has ineffective blood flow, does not negatively impact blood flow in that area.
My child’s doctor is recommending we remove her toes? How do I make the decision to amputate toes or alter her feet?
The decision to surgical alter a child’s foot is often a challenge for parents, to make. Often the recommendation to remove toes or change the shape of feet is made if:
- the surgery will improve function (ie – walking, running) or
- the surgery is restorative (helps child to fit into shoes, increase symmetry between feet).
Many of our families and children have been through this process, and are willing to discuss their experiences
I just found out through my child's quarterly ultrasound screening, that my child has cysts on her kidneys. What do we do next?
What we know is that there are a few abnormal kidney findings in people with CLOVES including difference in sizes, cysts, unusual architecture and Wilms tumors (see section above on WIlms tumor). New or changing kidney abnormalities should be reviewed by a Multi-disciplinary Vascular Anomalies Center with expertise in CLOVES, to help determine their significance.
Can you explain the difference between a clinical syndrome (CLOVES) vs. a genetic mutation (PIK3CA mutation)?
Many medical diagnoses start out being described as clinical syndromes. These syndromes are defined when doctors notice common features in patients and guess from that that the people probably have the same underlying thing going on. CLOVES started out as a clinical syndrome in this way. Before there was any knowledge of a gene or anything else, Dr. Ahmad Alomari noticed common features of patients and thought they must have something in common with each other. He named the syndrome CLOVES after the features the people had in common. In order to be diagnosed with CLOVES, in general you must demonstrate the symptoms given by the acronym CLOVES. Your condition must be Congenital (you have symptoms when you are first born), Lipotamous (has to do with fat), Overgrowth (some parts of your body are larger), Vascular (veins,arteries and lymphatics are involved), Epidermal Nevi (a type of birth mark on the skin), and skeletal (you have scoliosis or other skeletal abnormalities).
Like with lots of other clinical diseases or syndromes, once it's described, and especially now that we have the ability to do so, people have found a gene that's linked to CLOVES, but having CLOVES remains something that's diagnosed by having the physical features above. While a mutation in PIK3CA may confirm or be consistent with the diagnosis of CLOVES, it is not required to make this diagnosis. Some CLOVES patients do not have this mutation, but likely have mutations in related genes.
Why doesn’t a blood test show PIK3CA mutation?
The short answer: the mutation isn’t in every cell of a patient with CLOVES, but only in involved tissues. The mutation was first described in fatty masses (lipomas) after removal. When blood or a cheek swab are sent for genetic testing, this only analyzes the DNA in the cells from the blood or cheek lining. There is work underway using super-sensitive technology to try to identify the mutation from a blood test, which may be possible for some patients. If the blood test is negative, testing affected tissue would then be needed.
The PIK3CA mutations in CLOVES are “somatic” mutations. This means that CLOVES is not inherited and cannot be passed to future children. The mutation only exists in some tissues, generally the abnormal tissues in patients with CLOVES.
Click here to see an image description of a somatic mutation in CLOVES. These mutations were discovered in resected fatty tissues (lipomas) in patients with CLOVES.
No one knows why these genetic changes happen in CLOVES. For example, identical twins are actually not genetically identical. There are hundreds (at least) of genetic differences between identical twins as a result of mistakes copying DNA each time a cell divides. The vast majority of these genetic changes are silent and irrelevant, but occasionally one causes a disease. If a genetic change in PIK3CA occurs in one cell in a 100 cell embryo, this may explain the genetics of CLOVES. One could imagine that this genetic change could occur earlier (1 in 20 cells) in patients with more of their body affected by CLOVES, or later (1 in 400 cells) in patients with milder disease features.
My child is diagnosed with CLOVES. Why did her tissue biopsy come back negative for PIK3CA??
Since people with CLOVES still have mostly normal, healthy cells, if we want to diagnose CLOVES we have to look for cells which are most likely to have the CLOVES mutation. The best way to do that is to take a biopsy of affected tissue and search there. However, even in affected tissue the percentage of cells with the CLOVES mutation may still be low. Also, now most physicians only look for PIK3CA mutations in patients with CLOVES. A minority of patients with the clinical syndrome of CLOVES will have mutations in other, often related genes.
Some guidance on how to test for genetic changes in CLOVES
- Test affected tissue after biopsy or removal for known PIK3CA mutations. This can be done in a research setting, then confirmed clinically, or in a clinical lab.
- If negative, consider research testing of affected tissue. This may be more sensitive and may look for other mutations. Sometimes this involves looking harder at the PIK3CA and related genes. This can also include whole exome or whole genome sequencing where all genes are studied.
- If no biopsy or resection has occurred, consider blood (or even urine) testing in a research lab. If negative, testing of affected tissues will still be needed.
Is CLOVES Syndrome Community part of CLOVES Syndrome Foundation?
Great question!! CSC and CSF are two separate organizations.
CLOVES Syndrome Community was developed in 2009 with the mission of: support, education, empowerment and improvement of the lives of those affected by CLOVES Syndrome. We believe that when parents and loved ones are informed, empowered, and connected with others facing similar challenges, they will be better equipped to support their own or their child’s medical, emotional, and physical needs. CLOVES Syndrome Community was determined to be a 501C3 (Non Profit Public Charity) Organization by the Internal Revenue Service in July of 2011.
CLOVES Syndrome Foundation raises money for CLOVES research.
You can learn more about CLOVES Syndrome Foundation and the great work that they do at www.clovesfoundation.org.
Where can I learn more about CLOVES?
CLOVES Syndrome Community is grateful for our Medical Advisory Board, who help us to navigate the medical aspects of this syndrome. We are constantly updating information on the website and via social media, as more is discovered about CLOVES.
Sign up for our mailing list to be informed of the latest news and local events.
If you or someone in your family has been diagnosed with a CLOVES Syndrome, please message our Facebook fan page
(https://www.facebook.com/CLOVEsSyndromeCommunity) and "friend" our welcome account at https://www.facebook.com/WelcometoCLOVESCommunity.
Our support group setting on Facebook is set to "Secret" making it invisible on Facebook searches.
Joining our CLOVES community group will give you the opportunity to connect with many of the people diagnosed with this rare disease to share information and support.
Check out our to CLOVES Facebook Page to share information and raise awareness about CLOVES with friends and family, and Children’s Hospital Boston has CLOVES page
If you have any other questions that were not answered here, please email us at firstname.lastname@example.org