CLOVES syndrome

CLOVES syndrome is a complex condition characterized by congenital lipomatous overgrowth, mixed vascular malformations, epidermal nevi, and skeletal anomalies. Variants in the PIK3CA gene are linked to the abnormal cellular signaling that leads to the overgrowth and malformations observed in this condition. It typically presents sporadically without a clear family history and is known to be very rare, affecting fewer than 1 in 1 million people. Early recognition of characteristic physical findings can prompt appropriate evaluation and management.

Individuals with CLOVES syndrome most consistently exhibit features such as hemihypertrophy, capillary and venous malformations, lower limb asymmetry, and the presence of lipomas. These hallmark findings are often evident at birth, prompting further investigation, and may be accompanied by additional features including macrodactyly, scoliosis, renal hypoplasia, and a sandal gap in a significant number of cases, while others like webbed neck, nephroblastoma, spinal dysraphism, tethered cord, and splenomegaly occur less frequently. Not all individuals experience all features, and severity varies considerably. The constellation of symptoms is typically noted during early life, with ongoing monitoring important as new complications may emerge over time.

The genetic basis of CLOVES syndrome involves variants in the PIK3CA gene, which plays a crucial role in cellular growth and proliferation through the PI3K signaling pathway. Disruption in the pathway can lead to abnormal cell growth and the characteristic overgrowths and malformations observed in this condition. CLOVES syndrome arises in a multifactorial and sporadic manner, meaning that the genetic changes occur de novo in the affected individual without a clear familial pattern. Families are encouraged to seek genetic counseling to understand the implications and discuss any concerns related to the condition.

Currently, management of CLOVES syndrome focuses on supportive care and symptom management, with treatment tailored to the individual’s specific needs. A multidisciplinary team is typically involved in addressing the various aspects of the condition, including surgical interventions, monitoring of overgrowths, and management of vascular malformations. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients should discuss treatment options with their healthcare team and consider genetic counseling to better understand management strategies for their situation.

The clinical course of CLOVES syndrome is highly variable, with some individuals experiencing a relatively stable condition and others developing progressive complications over time. With current standards of care, many individuals can achieve a good quality of life, although outcomes depend on factors such as the severity of symptoms, age at diagnosis, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors to explore appropriate support and management options.

Several clinical trials are currently investigating new treatment approaches for CLOVES syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team regarding eligibility.