All you need to know about: CLOVES Syndrome

The Hindu

15 hours ago

CLOVES Syndrome, in which the letters stand for: Congenital; Lipomatous; Overgrowth; Vascular malformations ; Epidermal nevi and Spinal/skeletal anomalies/Scoliosis, is very a rare condition, with only about 200 cases or less are believed to have been reported worldwide.
Here is all you need to know about it.
What is CLOVES syndrome?
CLOVES Syndrome is a rare genetic disorder. Researchers believe it is caused by mutations in a gene called PIK3CA. According to the National Cancer Institute, U.S., this gene makes one of the proteins in an enzyme called PI3K, which is involved in many important functions in a cell. 'Mutations (changes) in the PIK3CA gene may cause the PI3K enzyme to become overactive, which may cause cancer cells to grow. PIK3CA gene mutations have been found in many types of cancer, including cancers of the breast, lung, ovary, stomach, brain, colon, and rectum. They have also been found in some genetic conditions,' the website states.
CLOVES Syndrome is an overgrowth disorder, part of a larger group of similar disorders called PIK3CA-related overgrowth spectrum or PROS.
When was it first discovered?
The U.S.-based non-profit National Organisation for Rare Disorders (NORD) states that CLOVES syndrome was described independently by [Julie C.] Sapp and colleagues in 2007 and [Ahmad I.] Alomari in 2009, making it a relatively new classification. The website however notes that a case report by the German physician Hermann Friedberg, 'gigantism of the right lower limb' published in 1867 is probably the first known written account of CLOVES syndrome.
Who is at risk?
The mutations in the PIK3CA gene are believed to occur spontaneously in the womb. CLOVES syndrome is not hereditary and cannot be passed on. At present, there are no known risk factors.
As per the NORD, it is believed that mutations in the gene result in two sets of cells in the body (one set with the mutation and one set without) and the mutated cells lead to the formation of abnormal tissue. It also states that CLOVES syndrome affects males and females equally regardless of their race or ethnicity.
What are the signs and symptoms of CLOVES syndrome?
Babies are born with this condition. Symptoms can range from mild to severe and may vary from child to child. Symptoms include: soft masses of fatty tissue on the abdomen, back, sides and buttocks; vascular or blood vessel anomalies such as dilated veins that may be seen in the chest, arms and legs and that may pose a risk of blood clots; large and wide hands or feet, with large gaps between fingers and toes; 'port wine stain' birthmarks; spinal problems such as scoliosis or a tethered cord; kidney problems; skin abnormalities such as raised bumps, and sometimes, intestinal problems and asymmetry in growth.
How is CLOVES syndrome diagnosed?
Doctors may diagnose CLOVES syndrome with a detailed physical examination, medical history and through various imaging tests such as MRIs, CT scans, ultrasounds and X-rays. A confirmation of the diagnosis can be made with molecular genetic testing for the mutation.
Not all patients with CLOVES syndrome will have all the signs, and some signs may be subtle. Detailed, expert medical examinations are necessary.
With the condition being so rare however, many healthcare providers are often not aware of it. Children with CLOVES syndrome are often misdiagnosed as having other syndromes.
How is CLOVES syndrome treated?
There is no cure as yet for CLOVES syndrome. However, with the right diagnosis, healthcare providers can help patients manage symptoms. Treating CLOVES syndrome usually involves a multidisciplinary team of specialists. Treatment options may include: drugs, to suppress the immune system and slow growth of abnormal vessels; sclerotherapy, which helps reduce the size of vascular malformations; embolisation, a minimally invasive procedure that blocks blood vessels and debaulking surgery to help remove overgrown tissue. Other orthopaedic or neuro surgeries may be required too. Rehabilitation therapies may also be prescribed.
What is the scenario in India?
A few cases of CLOVES syndrome have been documented in India. In 2019, Vikram K. Mahajan et al, wrote in the Indian Dermatology Journal Online of a three-year-old boy believed to have the syndrome. Another case of an eight-year-old boy was described by Pallavi Hegde et al in the Indian Journal of Paediatric Dermatology in 2022. Yet another case, of a 10-month-old boy was described by Ankur Singhal et al in the Indian Journal of Postgraduate Dermatology in 2024. The paper noted, 'CLOVES syndrome is exceptionally rare, and research in this area is predominantly limited to a scant body of published literature... We are presenting this case to contribute to medical literature by providing a comprehensive account on CLOVES syndrome.'