CLAPO syndrome (CLAPO: Capillary malformation of the lower lip, Lymphatic malformation of the face and neck, Asymmetry of face and limbs, Partial/generalized Overgrowth) is characterized mainly by localization of vascular and soft tissue anomalies in the head and neck region.
CLAPO syndrome also belongs to the large group of PROS (PIK3CA-related overgrowth spectrum) and is based on a genetic mosaic. It is caused by somatic (present only in the affected tissue) autosomal dominant gain-of-function mutations in the PIK3CA oncogene. Mutational constitutive activation of PIK3CA leads to overactivation of the PI3K(phosphatidylinositol 3-kinase)/AKT/mTOR pathway and causes enhanced cell growth and anti-apoptosis.
A particular feature of CLAPO syndrome that distinguishes it from other partial overgrowth syndromes is the capillary malformations (CM) of the lower lip and the relatively symmetric, bilateral or midline appearance of the vascular malformations. Although not initially claimed as a major feature of CLAPO syndrome, venous malformations (VM) are also among the more common vascular changes. Combined capillary-lymphatic-venous malformations are predominant and may be present at birth, especially at the tip of the tongue. Lymphatic malformations (LM) have been described in detail in only a few patients, then predominantly as (micro)cystic LM in the oro-facio-cervical region; lymphedema in the extremities occurs less frequently.