What is CLOVES Syndrome?

CLOVES syndrome is an extremely rare overgrowth disorder. Only 130-200 cases have been reported worldwide, and it was only recently delineated. Caused by a genetic mutation in the PIK3CA gene, the treatment and outcomes of this disorder depend on how early it was detected and diagnosed.

In this article, we will cover what CLOVES syndrome is, its signs and symptoms, and how it is diagnosed.

What is CLOVES Syndrome?

CLOVES syndrome is a rare genetic disorder thought to be caused by genetic mutations in a gene called PIK3CA. A combination of abnormalities in the bones, joints, skin, spine, or vascular system primarily characterises it.

The name stands for:

C – This stands for congenital, meaning it is present at birth.
L – This stands for lipomatous, which refers to lipomas, the soft fatty masses on the sides of the back and belly.
O – This stands for overgrowth, referring to the growth of fatty tissue in some areas, which grows much faster than in others.
V – V refers to vascular malformations. These include problems with blood vessels and lymph nodes.
E – E refers to epidermal nevi or skin lesions.
S—Lastly, S refers to spinal/skeletal anomalies, including scoliosis.

CLOVES disease and other conditions similar to it are known as overgrowth disorders. These disorders are part of a wider group known as PROS, or PIK3CA-related overgrowth spectrum.

What are the Causes of CLOVES Syndrome?

Genetic mutations in the PIK3CA gene cause CLOVES syndrome. Gene mutations like this can happen on their own for no known reason, a condition known as sporadic mutation. CLOVES syndrome is not hereditary, meaning it cannot be passed on from parents to children.

What are the Signs and Symptoms of CLOVES Syndrome?

CLOVES disease is a congenital condition, meaning it is present at birth. While symptoms may not always be noticeable right away, depending on the extent of the visible symptoms, it is usually diagnosed at birth. They also vary in terms of severity. While some children may display only mild symptoms, others display more extreme and life-threatening problems as a side effect.

Some signs to look out for in infants and children include:

1. Fatty Masses

CLOVES syndrome may manifest as masses of fatty tissue on the back, stomach area, or sides of the body.

2. Problems with Feet and Hands

This may present as large, wide feet and hands, large toes or fingers, or unusual spacing between the fingers and toes.

3. Dilated Veins

Dilated veins can occur in the chest, arms, legs, and feet, and there is also a risk of blood clots.

4. Birthmarks and Skin Abnormalities

Unlike regular birthmarks, birthmarks caused by CLOVES disease include flat or raised brown or red areas or are present as port-wine stains.

5. Scoliosis and Symmetric Growth

A sign of CLOVES could be spinal curvature, also known as scoliosis. It could also cause a tethered cord, where the spinal cord is attached to the spinal column.

6. Kidney and Other Organ Problems

While this symptom is less common, CLOVES can cause kidney abnormalities. They may be unusually large, asymmetric, or have Wilms tumours. Intestinal and bladder problems, such as bleeding, may also present.

CLOVES Syndrome Diagnosis and Treatment

Medical professionals typically diagnose this condition at birth. However, since CLOVES syndrome is so rare, it is still unknown to many healthcare providers. Doctors usually start by obtaining a detailed family and medical history, followed by a physical exam and imaging tests. It can require extensive examination and advanced imaging tests like MRIs, CT scans, or ultrasounds.

Fetal diagnosis is also possible in some instances. Genetic tests are also available to test for underlying mutations in the genes. The genetic test requires a biopsy using a small piece of abnormal tissue.
CLOVES syndrome can have symptoms similar to those of other disorders. For this reason, doctors typically look for a combination of problems concerning the spine, skin, and vascular system.

While there is no cure for CLOVES, treatment and early detection are vital to controlling its symptoms and side effects. Treatment methods include medical therapy, sclerotherapy, interventional radiology procedures, embolization, debulking surgeries, general surgery, orthopaedic procedures, neurosurgery, and other rehabilitation therapies, including physical and occupational therapy.

First described as a unique genetic condition in 2009, CLOVES syndrome is still being researched. CLOVES Syndrome Awareness Day is celebrated every August 3 to raise visibility for this condition. Early detection and diagnosis in children are crucial to creating a long-term treatment plan.

If an infant or child displays symptoms, it is important to start collecting family medical history and consult a medical professional. If CLOVES syndrome is suspected, further testing and imaging will be done before a diagnosis is declared. Visit Dr. Lal PathLabs for a CT scan or MRI examination and ensure your health is thoroughly assessed.