CLOVES Syndrome in an Indian Infant: A Comprehensive Case Report with Radiological Correlation and Review of the PIK3CA-Related Overgrowth Spectrum

Background: CLOVES syndrome (Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, and Spinal/Skeletal abnormalities) is an ultra-rare congenital overgrowth disorder belonging to the PIK3CA-related overgrowth spectrum (PROS). With fewer than 200 comprehensively documented cases worldwide and an estimated incidence of less than 1 per 1,000,000, reports from the Indian subcontinent remain exceedingly scarce. Early recognition is paramount to prevent irreversible neurological sequelae and life-threatening thromboembolic complications. Case Presentation: We report an 8-month-old male infant who presented with progressive right-sided asymmetric overgrowth, right pinna enlargement, and right-sided truncal and gluteal hypertrophy. Whole-body magnetic resonance imaging revealed extensive retroperitoneal, pelvic, paraspinal, and subcutaneous lipomatosis; epidural lipomatosis in the lumbo-sacral spine with severe thecal sac compression demonstrating the pathognomonic “Y-sign”; right renal hypertrophy with lobulated surface; asymmetric muscular hypertrophy of the right gluteal and thigh regions; and posterior sacral element defects with continuity of intraspinal and paraspinal fat. Brain imaging demonstrated mild paucity of white matter in the posterior centrum semiovale with supratentorial atrophic changes. The radiological impression initially favoured Proteus syndrome; however, clinico-radiological correlation established a diagnosis of CLOVES syndrome, and PIK3CA gene mutation analysis was recommended for molecular confirmation. Conclusion: This case underscores the diagnostic challenge of differentiating CLOVES from Proteus syndrome and highlights the critical importance of congenital onset, truncal lipomatous distribution, and the characteristic spinal epidural lipomatosis with Y-sign in establishing the correct diagnosis. We present a comprehensive review of the existing literature on CLOVES syndrome, emphasising current understanding of its molecular pathogenesis, thromboembolic risk profile, and the paradigm shift toward targeted PI3Kα inhibitor therapy. This report adds to the sparse literature from the Indian subcontinent and advocates for multidisciplinary surveillance in affected children.