CLOVES Syndrome

Congenital Lipomatous Overgrowth, Vascular anomalies, Epidermal nevi, and Skeletal deformities (CLOVES) syndrome is caused by a gain-of-function mutation in PIK3CA, which leads to overactivity of the mammalian target of rapamycin complex pathway. Characteristic cutaneous malformations help suggest the diagnosis and differentiate it from other conditions. Clinicians should consider genetic testing for CLOVES syndrome when encountering key clinical features such as congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal anomalies. Other characteristic features include segmental asymmetric limb growth, skin anomalies like capillary, venous, or lymphatic malformations, and renal anomalies. The presence of any of these signs should raise suspicion and warrant further investigation through genetic testing and imaging studies.