CLAPO syndrome is a subtype of the PIK3CA-related overgrowth spectrum (PROS) that results from the activation of somatic mosaic mutations in genes related to the PIK3CA pathway. Its name reflects its key characteristic features, which are a capillary malformation of the lower lip, a lymphatic malformation predominant on the face and neck, asymmetry, and partial / generalized overgrowth.

The capillary malformation of the lower lip is usually seen at birth. It involves the midline and is symmetrical and sharply defined. In some cases, only inner labial involvement without cutaneous involvement is seen. Typically, the capillary malformation usually stays stable without treatment or decreases in intensity over time.

The lymphatic malformation may be seen on the face and/or neck with a predisposition for the submandibular and parotid regions. More rarely, it involves an extremity. Complications may include bleeding, secondary infection, localized lymphedema, and jaw malocclusion. Other complications, such as macroglossia, dysphagia, and respiratory distress, can be seen with microcystic lymphangioma affecting the tongue and oral cavity. Lymphatic malformations are not always present at birth and may emerge later. Ninety percent of cases occur within the first 2 years of life.

Asymmetry is often the result of lymphatic malformation, but it may also occur on the limbs secondary to bone hypertrophy. Overgrowth typically appears later in life.