What is Cloves Syndrome

CLOVES syndrome is a rare overgrowth disorder characterized by congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies. It is caused by somatic mutations in the PIK3CA gene, leading to excessive cell growth and tissue development that typically manifests at or shortly after birth.

What are the primary symptoms of CLOVES syndrome?

CLOVES syndrome is an acronym that describes the core features of the condition. Patients often experience a combination of symptoms involving multiple body systems, including:

• Congenital Lipomatous Overgrowth: Fatty tissue masses that are present at birth or early infancy.


• Vascular malformations: Abnormal connections of blood vessels, such as capillary, venous, or lymphatic malformations.


• Epidermal nevi: Skin lesions that may appear as raised, darkened, or velvety patches.


• Spinal/skeletal anomalies: Scoliosis, wide feet, or abnormal bone growth in the limbs.

What causes CLOVES syndrome?

CLOVES syndrome is caused by a somatic activating mutation in the PIK3CA gene. Unlike inherited genetic conditions, these mutations occur after conception (post-zygotic), meaning they are not passed down from parents. This mutation leads to overactivation of the PI3K/AKT/mTOR signaling pathway, which acts like an "accelerator" for cell division and growth, resulting in the characteristic tissue overgrowth seen in CLOVES syndrome patients.

How rare is CLOVES syndrome?

CLOVES syndrome is an extremely rare disorder, with exact prevalence numbers difficult to determine due to historical underdiagnosis. It affects both males and females equally, with no known geographic or ethnic predilection. Currently, our DiseaseMaps.org community includes 7 individuals who have shared their experiences living with CLOVES syndrome, highlighting the importance of global collaboration in understanding this rare condition.

How is CLOVES syndrome different from other overgrowth disorders?

CLOVES syndrome is frequently compared to other PIK3CA-related overgrowth spectrum (PROS) conditions. It is specifically distinguished from conditions like Klippel-Trénaunay syndrome by the presence of specific spinal anomalies and the distinct pattern of lipomatous overgrowth. A clinical geneticist can help differentiate CLOVES syndrome from other syndromes through targeted genetic testing and physical evaluation.

Next steps

• Consult with a geneticist or a specialist in vascular anomalies to confirm a diagnosis of CLOVES syndrome.


• Connect with the DiseaseMaps.org community to share experiences with others managing CLOVES syndrome.


• Monitor for new symptoms through a multidisciplinary care team, including orthopedists, dermatologists, and vascular specialists.

Medical disclaimer: This information is for educational purposes and should not replace professional medical advice, diagnosis, or treatment; always seek the guidance of your physician regarding any medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): CLOVES syndrome overview.


• Orphanet: Rare disease database entry for CLOVES syndrome.


• OMIM (Online Mendelian Inheritance in Man): Entry #612918 regarding PIK3CA-related overgrowth.


• The CLOVES Syndrome Community: Patient-led advocacy and research resources.