In Cloves syndrome, PIK3CA gene mutations cause overgrowth of lipomas as well as vascular abnormalities and nevi on the skin.
Cloves syndrome or Clove Syndrom (congenital overgrowth of lipomas, vascular abnormalities, nevi on the skin, and lateral curvature of the spine and skeletal system) is a genetic disorder caused by somatic mutations in the PIK3CA gene.
It belongs to the spectrum of overgrowth syndromes related to this gene, called PROS for short. It is reported that there is no specific treatment for this rare condition, and the survival rate of those affected is poor.
Scientists describe a postnatal mouse that had PROS/CLOVES syndrome that partially recapitulates human disease and demonstrates the efficacy of BYL719, a PIK3CA inhibitor. In preventing and improving organ dysfunction. Based on these findings, the researchers used BYL719 to treat 19 patients with PROS syndromes.
The drug improved the symptoms of the disease in all patients, and the previously intractable blood vessel tumors became smaller. The incidence of congestive heart failure improved. The hemihypertrophy decreased, and the severity of scoliosis was reduced. The treatment was not accompanied by any severe side effects.
Finally, this study provides the first direct evidence to support PIK3CA inhibition as a promising treatment strategy for people with cloves syndrom.
What is Cloves syndrome?
Clove syndrome is a very rare genetic disorder. Its name is because of the combination of abnormalities of the blood vessels, skin, spine, bones, or joints that make up the syndrome:
- C: Congenital (present at birth)
- L: lipomas (referring to lipomas, soft lumps of fat often found on one or both sides of the back and abdomen)
- O: Overgrowth (fatty tissue in some areas of the body, which grows more quickly than others)
- V: Vascular malformations (problems with lymphatic and blood vessels)
- E: epidermal nevus (skin lesions)
- S: spinal/skeletal abnormalities and/or scoliosis (tethered spinal cord)
Clove and other rare conditions that can cause similar symptoms are overgrowth disorders. These are part of a larger group of similar disorders called PIK3CA-associated overgrowth spectrum (PROS).
What Are The Signs And Symptoms of Clove Syndrome?
Babies with CLOVES syndrome are born with this condition. It may cause:
- Lumps of fatty tissue on the abdomen, back, or sides
- Problems with the feet and hands (oversized hands and feet; fingers or toes; unusual spacing between toes and hands)
- Dilated veins (chest, arms, legs, and feet with risk of blood clots)
- Birthmarks (flat or raised areas that are red or brown, port wine spots)
- Spinal curvature (scoliosis) or cord tethered (when the spinal cord is attached to the spine)
- Kidney problems (unusual size, asymmetry, Wilms tumor)
- Intestinal and bladder problems (bleeding)
- Asymmetric growth (one side grows faster than the other, such as arms, legs, or head)
- Symptoms of clove syndrome vary widely in structure and severity. Some children have mild symptoms, while others can have serious, life-threatening problems.
Not everyone with CLOVES syndrome will have all of these symptoms, but there is a combination of them. In addition, symptoms of CLOVES syndrome can vary from mild to severe.
Causes of Cloves Syndrom:
CLOVES syndrome is often happen by a genetic mutation (change) that occur during a baby’s early development in the womb. Genes are responsible for determining the traits of a person.
In CLOVES syndrome, a change occurs in the gene known as PIK3CA. It is a growth regulator gene, which means that it plays an important role in directing 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 sebaceous tumors and other problems.
Although it is linked to a genetic mutation, CLOVES syndrome is a non-genetic disorder, which means it is not passed from father to child. In the case of CLOVES, the PIK3CA gene is mutated on its own without a known cause. Experts call this sporadic boom.
Diagnose of Cloves Syndrome
To diagnose CLOVES syndrome, a doctor will start by looking for a distinct group of skin, blood vessels, and spinal problems. This will be complete through a physical examination.
From there, the suspect diagnosis of CLOVES syndrome will be confirm by the following methods:
- Imaging: An X-ray or MRI gives the doctor an inside view of any tissue or bone abnormalities in the chest, stomach, pelvis, spine, and extremities.
- Ultrasound: High-frequency sound waves are helpful to examine organs in the abdomen, such as the kidneys. It can detect changes in size or shape in organs, tissues, and blood vessels, and may show whether there is a tumor mass. Ultrasound may also be helpful to check for CLOVES syndrome before birth (while the baby is still in the womb).
- Genetic testing: Also known as a DNA test, sometimes a blood test can be helpful to confirm a mutation in the PIK3CA gene that causes CLOVES syndrome. However, this test is not always in use, because experts have found that it is not always accurate. No DNA test is necessary to diagnose CLOVES syndrome.
Treatment of Cloves Syndrome
There is currently no cure for CLOVES syndrome, but a team of doctors can help treat and manage the various symptoms it causes.
Treatment plans vary by person, but can usually include:
- Medications: An oral immune system medication called sirolimus can help control some blood vessel abnormalities.
- Sclerotherapy and embolization: These minimally invasive procedures help shrink enlarged blood vessels and block blood flow to the fat tumor.
- Slimming surgery and general surgery: Surgery is often helpful to remove an overgrowth of fatty tissue.
- Orthopedic procedures: Orthopedic surgeries can help correct any abnormalities in the limbs or joints.
- Neurosurgery: Surgery can help repair a tethered spinal cord or a mass of tissue that has formed around or around the spine.
- Rehabilitation therapies: Physical and occupational therapy are often treatment options for patients who have had surgeries or procedures.
- Regular ultrasound: Beginning at age eight, experts recommend a kidney scan to check for Wilms’ tumor.
Early diagnosis is very important for children with cloves syndrom. Evaluation and treatment with a multidisciplinary team that specializes in Vascular malformations should begin as soon as possible to help manage the child’s specific symptoms and health.
