Proteus-like syndrome

Proteus-like syndrome is a rare overgrowth condition that shares clinical features with Proteus syndrome but does not meet the strict diagnostic criteria established for classic Proteus syndrome. Patients with Proteus-like syndrome exhibit progressive, disproportionate, and asymmetric overgrowth of various tissues, including bone, skin, connective tissue, and adipose tissue. The condition can affect multiple body systems, leading to skeletal abnormalities such as limb length discrepancy and macrodactyly, vascular malformations, lipomas or lipomatosis, epidermal nevi, and connective tissue nevi. Some patients may also develop visceral abnormalities. The overgrowth is typically mosaic in distribution, meaning it affects some areas of the body but not others, and tends to be progressive over time. The clinical presentation can be highly variable between individuals, which contributes to diagnostic challenges. Features may overlap with other segmental overgrowth syndromes, including PIK3CA-related overgrowth spectrum (PROS) and other mosaic conditions involving the PI3K/AKT/mTOR signaling pathway. Advances in molecular genetics have shown that some patients previously classified as having Proteus-like syndrome carry somatic mutations in genes such as PIK3CA rather than the AKT1 mutation characteristic of classic Proteus syndrome. Management is primarily symptomatic and supportive, involving a multidisciplinary team. Surgical interventions may be necessary to address significant overgrowth, skeletal deformities, or vascular malformations. Emerging targeted therapies, such as mTOR inhibitors (e.g., sirolimus) and specific PI3K inhibitors (e.g., alpelisib), are being investigated and may offer benefit in selected cases, though evidence remains limited for this specific diagnostic category.

Common questions about Proteus-like syndrome