CLAPO syndrome

What is CLAPO syndrome?

CLAPO syndrome is a rare genetic vascular disorder characterised by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalised overgrowth.

This condition is also known as Lopez-Gutierrez syndrome.

Who gets CLAPO syndrome?

CLAPO syndrome arises from a sporadic somatic mutation and is not inherited. It has an estimated prevalence of less than 1 in 1,000,000, with no known gender or racial predilection.

What causes CLAPO syndrome?

CLAPO syndrome is caused by somatic gain-of-function mutations of the PIK3CA (phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha) gene, which is responsible for regulating cell division and growth.

CLAPO syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS), alongside conditions such as MCAP and CLOVES syndrome.

What are the clinical features of CLAPO syndrome?

• Capillary malformation of the lower lip
  • Hallmark feature
  • Typically present at birth and does not exhibit progression
  • Found in the midline
  • Symmetrical and sharply defined
• Lymphatic malformation
  • Most commonly occur in the submandibular and parotid region
  • Can emerge later in life
  • May be associated with lymphoedema of the extremities
• Asymmetry
  • Secondary to lymphatic malformations of the face and neck
  • Can also result from bone hypertrophy, which usually develops later in life
• Partial or generalised overgrowth
  • Soft tissues and bone affected

How do clinical features vary in differing types of skin?

For people with darker skin tones, capillary malformations may be less visible but can be distinguished by their maroon colour.

What are the complications of CLAPO syndrome?

The complications of CLAPO syndrome are usually related to the lymphatic malformations and include:

• Bleeding
• Swelling
• Infection
• Vesicle formation
• Malocclusion (misaligned bite)
• Macroglossia
• Dysphagia
• Respiratory distress.

How is CLAPO syndrome diagnosed?

CLAPO syndrome is primarily a clinical diagnosis based on the presence of key features, such as capillary malformation of the lower lip and lymphatic malformations.

Diagnosis is confirmed by genetic testing of affected tissue, revealing a PIK3CA gene mutation.

What is the differential diagnosis for CLAPO syndrome?

• Infantile hemangioma
• Sturge–Weber syndrome
• Parkes-Weber syndrome
• Proteus syndrome
• Conditions on the PIK3CA-related overgrowth spectrum (PROS):
  • MCAP
  • CLOVES syndrome
  • Klippel–Trénaunay syndrome.

What is the treatment for CLAPO syndrome?

General measures

Routine follow-ups in children with capillary malformation to prevent potential complications of lymphatic malformations.

Specific measures

• Capillary malformations can be treated with pulsed dye laser therapy.
• Lymphatic malformations can be treated with:
  • Sclerotherapy
  • Alpelisib (PIK3 inhibitor) and sirolimus (mTOR inhibitor) for symptomatic lesions
  • Resection and CO2 laser photocoagulation for lesions of the tongue.

How do you prevent CLAPO syndrome?

There is no known way to prevent CLAPO syndrome.

What is the outcome for CLAPO syndrome?

Early recognition and ongoing monitoring of CLAPO syndrome are essential to optimise treatment success and minimise the occurrence of potential complications. The capillary malformation can remain stable or even improve without treatment.