CLAPO syndrome

CLAPO syndrome is an extremely rare congenital vascular disorder whose name is an acronym for its defining features: Capillary malformation of the lower lip, Lymphatic malformation of the face and neck, Asymmetry of the face and limbs, and Partial or generalized Overgrowth. The condition is present from birth and primarily affects the vascular and lymphatic systems, with visible manifestations on the face, particularly a characteristic capillary malformation (port-wine stain) involving the lower lip, which is considered a hallmark feature. Lymphatic malformations, which are abnormal collections of lymphatic vessels, typically occur in the face and neck region and can cause significant facial asymmetry. Affected individuals may also demonstrate overgrowth of soft tissues and bones, leading to asymmetry of the limbs and body. CLAPO syndrome belongs to the broader group of vascular malformation-overgrowth syndromes, which includes conditions such as Klippel-Trenaunay syndrome and CLOVES syndrome. The underlying genetic cause has been linked to somatic (post-zygotic) activating mutations in the PIK3CA gene, placing it within the spectrum of PIK3CA-related overgrowth syndromes (PROS). Because these mutations arise during embryonic development and are present only in affected tissues (mosaic), the condition occurs sporadically and is not typically inherited from a parent. Diagnosis is based on clinical recognition of the characteristic combination of features, supported by imaging studies such as MRI to evaluate the extent of lymphatic and vascular malformations. There is currently no cure for CLAPO syndrome. Treatment is symptomatic and multidisciplinary, often involving dermatologists, vascular specialists, and surgeons. Management may include laser therapy (such as pulsed dye laser) for capillary malformations, sclerotherapy or surgical debulking for lymphatic malformations, and orthopedic interventions for limb length discrepancies or overgrowth. Targeted therapies such as sirolimus (an mTOR inhibitor) and alpelisib (a PIK3CA inhibitor) are being explored for PIK3CA-related overgrowth conditions and may offer benefit, though evidence specific to CLAPO syndrome remains limited.

Common questions about CLAPO syndrome