CLOVES syndrome is an extremely rare overgrowth disorder that has a unique combination of symptoms and is related to the mutation of a particular gene during prenatal development. Though the exact cause of the condition is not known, the condition has vascular anomalies, epidural lesions, fatty tissue growths, and spinal abnormalities associated with it.
Definition & Facts
CLOVES is an acronym for the conditions that present at the time of diagnosis:
- Congenital is a condition existing at or before birth.
- Lipomatous refers to the benign fatty tumors that form (lipomas)
- Overgrowth as pertaining to the abnormal size of affected areas.
- Vascular malformations. Patients present with different venous, capillary, and lymphatic channels, or slow flows.
- Epidermal naevi are chronic, benign lesions on the skin, which have a warty appearance.
- Spinal anomalies like a tethered spinal cord, spinal lesions, or scoliosis are also present.
CLOVES syndrome affects between 90 and 120 children worldwide.
Symptoms & Complaints
- Fatty masses in the child’s torso (abdomen, flank, or back).
- Port-wine stain birthmark, which is an indicator of vascular, lymphatic or arteriovenous malformation.
- Abnormalities of the limbs, such as large fingers or toes, extra fingers or toes (polysyndactyly), or extremely wide feet.
- Spinal issues. Abnormalities of the spine like scoliosis or a tethered spinal cord typically point toward a diagnosis of CLOVES even when the other symptoms present.
- Epidermal nevi are skin abnormalities that look similar to warts.
- Other symptoms can include knee problems and hip problems among other joint problems, or the presence of kidneys that are unusually small or not equal in size.
Though some of these symptoms present in the cases of other diagnoses, the combination of several of these symptoms usually points a physician toward a CLOVES syndrome diagnosis.
The exact cause of CLOVES syndrome is currently unknown. However, researchers at Boston Children’s Orthopedic Research Laboratories have discovered a correlation between a genetic mutation in a particular gene and the presence of CLOVES. According their research, CLOVES is genetic, but not hereditary and is connected to a genetic mutation rather than any particular trait that is passed on by the parents.
The gene that is mutating in the development of CLOVES is referred to as PIK3CA. It was discovered that between 6 and 60 percent of each individual’s effected tissues had a mutation of this gene present, though the precise mutation varied from one patient to the other. The mutations arise spontaneously in particular areas and in varying degrees during fetal development.
Though the discovery of this correlation has made researchers optimistic about pinpointing the cause, the reason why that particular gene mutates has still not been determined.
Diagnosis & Tests
The symptoms of CLOVES syndrome are often subtle and might not be noticed right away or they may be very obvious and cause problems for the effected child immediately. In either case, obtaining the proper diagnosis of the disease is critical. There are a particular set of tests that usually precede a diagnosis of CLOVES, including:
- An extensive family history and individual medical history
- A thorough medical examination (physical examination) of all affected areas.
- Magnetic resonance imaging (MRI) and computed tomography (CT) scans as well as medical ultrasounds and X-rays.
With the discovery of the PIK3CA gene’s contribution to the condition, DNA testing is being added to this list of tests as well, though the majority of pediatric and neonatal facilities are not yet aware of this connection to the condition.
Prenatal ultrasounds are able to detect CLOVES syndrome, however, because the condition is so rare, it is usually not something that doctors are looking for during in utero examinations. Consequently, most examinations of the condition do not take place until after birth.
Treatment & Therapy
Because the cause is not yet known, treating the underlying cause is not yet possible as well. However, there are a number of treatments and therapies that address the relief of the symptoms associated with CLOVES syndrome.
- Sclerotherapy. In this procedure, typically performed by a radiologist, a toxic agent, sclerosant, is injected into the malformation. The toxic agent causes the malformation to scar over with the hope of not only relieving the pain caused by the anomaly, but also shrinking its size.
- Embolization. This is a minimally invasive procedure in which a radiologist navigates a thin tube, a catheter, through the child’s arteries to the location of the arteriovenous abnormality. A substance is injected at that point in order to block a particular venous flow through the affected area.
- Debulking surgery. This is a major, invasive surgery that involves multiple, lengthy and complex procedures over a period of time. During those procedures a portion of the overgrown tissue and the related blood vessels are removed. Though it is an extensive option, it can have an enormous affect on the child’s life, especially in cases where the overgrowth causes pain or immobility
- Preventing pulmonary embolisms. Pulmonary embolisms are a significant risk to children with CLOVES and therefore great lengths are taken during surgery and other treatments to prevent those life-threatening blood clots from developing, breaking loose and traveling through the bloodstream. A device known as an inferior vena cava filter (IVC) is typically used for this purpose.
- Managing spine, bone/joint and kidney disease. A team of specialists referred by the child’s primary care physician will work on treating various issues related to the spine, bones, joints and kidney problems that are often associated with CLOVES symptoms.
Prevention & Prophylaxis