CLAPO syndrome is a very rare health condition that mostly affects the skin, blood vessels, lymph vessels, and the growth of some body parts. The name “CLAPO” is built from its main signs: Capillary malformation of the lower lip, Lymphatic malformation of the face and neck, Asymmetry of the face and limbs, and Partial or generalized Overgrowth. In simple words, a child is born with a red stain on the lower lip, soft swellings filled with fluid in the face or neck, body parts that are not the same size on both sides, and extra growth in some areas.
CLAPO syndrome is a very rare vascular overgrowth disorder where children (and sometimes adults) have a capillary malformation on the lower lip, lymphatic malformations of the face/neck, body asymmetry, and partial or generalized overgrowth. It belongs to the PIK3CA-related overgrowth spectrum (PROS), caused by somatic (mosaic) activating variants in the PIK3CA gene. [1] Because CLAPO is ultra-rare, there are no large randomized trials and no drugs approved “for CLAPO” specifically. Most treatments are adapted from vascular malformation and PROS guidelines, and many medicines are off-label. Management must always be guided by a specialist multidisciplinary team. [2]
Doctors now think CLAPO syndrome belongs to a bigger group of conditions called PIK3CA-related overgrowth spectrum (PROS). In this group, a change (mutation) in a gene called PIK3CA makes some cells grow too much and live too long. This extra growth can affect blood vessels, lymph vessels, fat, muscle, and bone. CLAPO is one special pattern inside this group, where the lower lip and nearby areas are mainly involved.
CLAPO usually shows at birth or in early childhood. The condition does not spread from person to person. It is very rare in the general population, with fewer than 1 person in a million affected. Because it is so rare, many doctors may not know it well, and children are sometimes misdiagnosed with more common vascular birthmarks at first.
Other names
CLAPO syndrome has several long medical names and short labels. These are different ways to describe the same condition:
Capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs, and partial/generalized overgrowth. This is the full descriptive name that explains all four main signs in detail.
CLAPO syndrome. This is the short name built from the first letters of the main signs. Doctors use it most often in clinics and research papers.
CLAPO. Sometimes only the acronym is used without the word “syndrome,” but it means the same thing and still refers to this specific pattern of problems.
Lopez-Gutierrez syndrome (proposed). In some places, the condition has been linked to the name of the doctor who first described it in a group of six children, but this name is not used as often as “CLAPO syndrome.”
All of these names refer to the same rare vascular overgrowth disorder, not to different diseases.
Types of CLAPO syndrome
There is no official, strict type classification for CLAPO syndrome yet, because only a small number of people have been reported. However, based on real patients, doctors and researchers sometimes describe helpful “forms” or patterns:
Classic CLAPO form. This form has all four key signs together: lower lip capillary stain, lymphatic malformations in face or neck, body asymmetry, and partial or generalized overgrowth of one or more segments.
CLAPO without clear overgrowth. Some people have the typical lower lip capillary malformation and lymphatic changes but show little or no obvious extra growth of limbs or trunk. Doctors still see this as part of the same spectrum.
CLAPO with marked overgrowth. In other people, one side of the face, one limb, or a larger body region can be much bigger than the other side, with fat, soft tissue, and sometimes bone overgrowth. This overlaps with other PROS conditions.
Localized CLAPO (segmental form). In some cases the changes are mostly limited to the lip and nearby tissues, with only small or subtle changes in the rest of the body. These patients are on the “milder” end of the spectrum.
CLAPO overlapping with other PROS disorders. Rarely, features of CLAPO can mix with signs of other PIK3CA-related overgrowth conditions, such as CLOVES or MCAP, making diagnosis more complex.
These “types” are mainly used to describe how strong and how wide the changes are in each person, rather than to define separate diseases.
Causes of CLAPO syndrome
Main idea about the cause
The main known cause of CLAPO syndrome is a somatic mutation (a change that happens after conception) in the PIK3CA gene in some cells of the body. This gene controls a pathway called PI3K-AKT-mTOR, which helps cells grow, divide, and survive. When this pathway is overactive, cells grow too much and form malformations and overgrowth.
Below are 20 key points that explain the cause and related mechanisms in simple words. Most of them are different ways of looking at the same basic genetic problem, because only one main root cause is known.
Somatic PIK3CA mutation. In CLAPO syndrome, a mistake appears in the PIK3CA gene in some cells of the baby during early development. This mistake is not present in every cell, only in parts of the body that later show overgrowth or malformations.
Mosaic pattern of changed cells. Because the mutation happens only in some cells, the body shows “patches” of abnormal tissue. This mosaic pattern explains why one lip, one side of the face, or one limb can look different from the other side.
Overactive PI3K-AKT-mTOR pathway. The PIK3CA mutation keeps this growth pathway “switched on” more than normal. This leads to extra cell growth and less cell death, so tissues become larger, thicker, or malformed.
Abnormal blood vessel growth. The overactive pathway makes small blood vessels, especially capillaries, grow in an abnormal way. On the lower lip this shows as a flat or slightly raised red stain called a capillary malformation.
Abnormal lymph vessel growth. The same pathway affects lymphatic vessels, which carry clear fluid in the body. These vessels can become enlarged, twisted, or form cyst-like spaces, creating soft swellings in the face, neck, or other areas.
Overgrowth of soft tissues. Fat, skin, and deeper soft tissues in the affected area can grow more than normal because the mutated cells keep dividing. This extra tissue makes the lip thicker or the face and limbs larger on one side.
Overgrowth of bone in some segments. In some patients, bone cells in the affected side also have the mutation, so bones can grow longer or thicker than on the other side, causing limb length differences or facial bone asymmetry.
Imbalance between growth and cell death. Normal tissue growth is a balance between cell growth and programmed cell death. In CLAPO syndrome, the PIK3CA mutation shifts this balance toward growth, so tissues accumulate rather than being trimmed back.
Very early timing in the embryo. The mutation occurs very early in the embryo’s life, before birth. The earlier it happens, the larger the body area that can be affected, which explains why some children have more widespread overgrowth than others.
Not usually inherited from parents. CLAPO syndrome is almost always sporadic, meaning it happens new in the child and is not passed down from the parents’ genes. The PIK3CA change is found only in the child’s mosaic tissues.
Chance (random) genetic event. Scientists think the mutation is mostly a random error in DNA copying during cell division, rather than something caused by a known outside exposure or the parents’ actions.
Local tissue environment. Once a group of cells carries the mutation, the surrounding tissue, blood supply, and lymph flow may also adapt in an abnormal way, helping the malformation grow and persist over time.
Link to the PROS family. CLAPO syndrome shares the same PIK3CA pathway problem as other PROS disorders (such as CLOVES and certain macrodactyly forms), which supports the idea that these are different faces of one basic biological error.
Possibility of different mutation strengths. Different exact changes in the PIK3CA gene can have stronger or weaker effects on the pathway. This may explain why some people have mild CLAPO features and others have more severe overgrowth.
Limited detection in blood. Because only some tissues carry the mutation, regular blood samples may not show it. Often, the gene change can only be found if doctors test the affected skin or overgrown tissue directly.
No clear link to pregnancy problems. Current reports do not show a strong link between CLAPO syndrome and infections, drugs, or obvious problems during pregnancy, again pointing to a random genetic event rather than an outside cause.
No simple lifestyle cause. Food, exercise, or normal environmental factors are not known to cause CLAPO syndrome. This can reassure families that nothing they did during pregnancy caused the condition.
Possible additional genetic changes. Some researchers suggest that, in rare cases, more than one gene change (“second hits”) might shape how severe the overgrowth is, but this has not been clearly proven yet.
Long-lasting but stable cells. The mutated cells remain in the body over time, so the malformations and overgrowth usually do not go away on their own. Growth may slow after childhood but the basic pattern stays.
Target for new drugs. Because the cause is an overactive PI3K-AKT-mTOR pathway, new targeted drugs against PIK3CA are being studied in PROS, including CLAPO, to try to reduce overgrowth and vascular problems by calming this pathway.
Symptoms of CLAPO syndrome
General symptom pattern
CLAPO syndrome symptoms come from three main problems: abnormal small blood vessels (capillary malformations), abnormal lymph vessels (lymphatic malformations), and uneven or extra growth of tissues. The exact mix of symptoms can be different in each person, depending on which body areas are affected.
Below are 15 common symptoms or clinical features, in simple language.
Red stain on the lower lip. Most people with CLAPO have a flat or slightly raised red or purple stain on the lower lip. It is caused by many tiny extra blood vessels close to the skin surface (capillary malformation).
Thick or swollen lower lip. The lip can look thick, puffy, or uneven because of extra soft tissue and abnormal blood or lymph vessels inside it. This can change the shape of the mouth and smile.
Soft swellings on the face or neck. Lymphatic malformations in the cheeks, chin, or neck can feel like soft, compressible lumps that may get larger with infections or changes in body fluid.
Visible small blisters or vesicles. In some cases, the skin over a lymphatic malformation can show small clear or blood-filled blisters that may leak fluid or bleed easily.
Asymmetry of the face. One side of the face can look bigger or fuller than the other because of extra fat, muscle, or bone growth, sometimes making the nose, lips, or chin look off-center.
Asymmetry of the limbs. One arm or leg can be longer, thicker, or both compared with the opposite limb. This is called hemihyperplasia or segmental overgrowth and can affect walking and posture in some children.
Partial or generalized overgrowth. Extra growth may be limited to one area (for example, one leg and part of the pelvis) or involve larger segments of the body, depending on where the mutated cells are located.
Heaviness or discomfort in enlarged areas. Overgrown limbs or tissues can feel heavy or tired, especially after standing or walking for a long time, because of the extra weight and abnormal blood and lymph flow.
Recurrent swelling attacks. Lymphatic malformations can suddenly swell more during infections, after minor injuries, or with hormonal changes, causing episodes of pain or tightness.
Skin infections or cellulitis. Areas with lymphatic malformations are prone to skin infections because the lymph fluid does not drain normally, which can let bacteria grow more easily.
Bleeding or oozing from lesions. Fragile blood vessels and surface blisters may bleed or leak fluid with small trauma, brushing teeth, or eating, especially when the lip or mouth is involved.
Problems with speech or eating. A very thick or uneven lower lip, or large masses in the mouth or neck, can make it harder to speak clearly, close the mouth, or chew and swallow food comfortably.
Breathing or airway problems (in severe cases). Large lymphatic malformations in the neck or near the airway can press on the windpipe and cause noisy breathing, snoring, or breathing trouble, especially when lying down or during infections.
Dental and jaw alignment issues. Overgrowth of the jaws or uneven growth of the facial bones can lead to crowded teeth, bite problems, or difficulty closing the lips together.
Emotional and social impact. Visible stains, swellings, and asymmetry of the face can affect self-esteem, cause teasing, and lead to anxiety or sadness, especially in school-age children and teenagers.
Diagnostic tests for CLAPO syndrome
How doctors make the diagnosis
There is no single blood test that alone proves CLAPO syndrome. Doctors use a mix of careful physical examination, detailed imaging of blood and lymph vessels, and sometimes genetic testing of affected tissue to confirm the diagnosis and to rule out other overgrowth or vascular conditions.
Physical examination tests
Full medical history and physical exam.
The doctor asks about pregnancy, birth, early growth, and any swelling or overgrowth problems, then examines the whole body from head to toe. They look for stains, swellings, and differences between the two sides of the body. This first step helps the doctor suspect CLAPO and plan which other tests are needed.Detailed skin and lip examination.
The doctor carefully inspects the lower lip, face, and neck to see the color, size, and borders of the capillary malformation, and to check for blisters or lymphatic changes on the skin. The look of the lower lip lesion is a key clue for CLAPO syndrome.Growth and body proportion measurements.
Height, weight, head size, and limb lengths are measured and compared with age charts. The doctor checks if one side of the face or one limb is bigger and if overgrowth is stable or changing over time. This helps to document asymmetry and overgrowth, which are part of the CLAPO picture.
Manual tests (done by hand at the bedside)
Palpation of lip, face, and neck lesions.
The doctor gently presses on the swellings and lip lesion with their fingers to feel if they are soft, firm, compressible, or filled with fluid. This simple test helps to tell lymphatic malformations (soft, cystic) from other types of lumps or tumors.Limb length and circumference measurement.
Using a measuring tape or blocks, the doctor checks the exact length and thickness of both arms and both legs. Small differences may be normal, but larger differences suggest segmental overgrowth linked to CLAPO or other PROS conditions.Joint movement and functional tests.
The doctor gently moves the joints of the affected limbs and asks the child to walk, run, or use the hands. This shows if overgrowth or swelling is limiting movement, balance, or daily activities like dressing and writing.
Lab and pathological tests
Basic blood tests (CBC and chemistry).
A complete blood count and simple blood chemistry are often done to look for anemia, infection, or problems with organs before any surgery or invasive procedure. These tests do not diagnose CLAPO directly but help to check general health.Coagulation (clotting) tests.
Because vascular malformations can sometimes affect blood clotting, doctors may check clotting time, fibrinogen, and D-dimer, especially if there is pain, swelling, or a plan for surgery. This helps to reduce bleeding risks.Biopsy of a skin or soft tissue lesion (if needed).
In some unclear cases, a small piece of the lip or skin lesion is removed under local or general anesthesia. The tissue is studied under a microscope to see the structure of capillaries or lymphatic spaces and to confirm that it is a vascular malformation, not a tumor.Histopathology of vascular and lymphatic malformations.
Microscopic study of the biopsy can show enlarged, irregular capillaries or dilated lymphatic channels, sometimes with features that match other PROS vascular anomalies. This supports the diagnosis and may guide treatment choices.Targeted PIK3CA genetic testing on affected tissue.
DNA from the biopsy or from a carefully taken skin or tissue sample is tested by high-sensitivity methods (such as next-generation sequencing) to look for PIK3CA mutations. Because the mutation is mosaic, testing affected tissue is often more successful than testing blood. Finding a PIK3CA mutation supports CLAPO as a PROS condition.Extended genetic panels or exome sequencing (selected cases).
In complex or unclear situations, doctors may use larger gene panels or exome sequencing to rule out other genetic overgrowth syndromes and to confirm that the changes fit the PROS group. This is usually done in specialized centers.
Electrodiagnostic tests (only when there are nerve or brain symptoms)
Electroencephalogram (EEG).
If a child with CLAPO has seizures, episodes of staring, or other suspected brain events, an EEG may be done to check the electrical activity of the brain. Seizures are not a classic sign of CLAPO itself but can appear in some PROS patients, so doctors may use this test when needed.Nerve conduction study and EMG.
When there is weakness, numbness, or abnormal limb function, nerve tests may be used to see if nerves or muscles are affected. This is not routine in CLAPO but can help rule out other causes of limb problems in selected patients.
Imaging tests
Soft tissue ultrasound.
Ultrasound uses sound waves to look at the lip, face, neck, and other swellings. It can show if a lesion is solid or cystic, if it is filled with fluid, and whether it looks more like a lymphatic or venous malformation. It is painless and has no radiation, so it is often used first, especially in children.Doppler ultrasound of blood flow.
Doppler ultrasound adds color flow mapping to see how blood moves through the vessels. It helps to confirm that the red lesion on the lip is a low-flow capillary malformation and to check for any abnormal draining veins.Magnetic resonance imaging (MRI).
MRI gives detailed pictures of soft tissues, including lymphatic malformations in the face, neck, chest, or abdomen. It shows how deep the malformation goes, what structures it touches, and whether it might press on airways or nerves. MRI is very important when planning surgery or other treatments.Computed tomography (CT) scan.
CT uses X-rays to give detailed images of bone and some soft tissues. It is sometimes used to measure bone asymmetry or when MRI is not possible, but doctors try to limit CT use in children because of radiation.Lymphoscintigraphy or MR lymphangiography.
These special imaging tests show how lymph fluid moves through the lymphatic system. They may be used when lymphatic malformations or limb swelling are severe, to map the abnormal lymph vessels and plan treatment like surgery or interventional radiology.X-rays for bone length and shape.
Simple X-rays of the legs, arms, or jaw can show differences in bone length and thickness between both sides and help track growth over time. This is useful for decisions about orthopedic treatment, such as limb length correction in older children.
Non-pharmacological treatments (therapies and other measures)
Because CLAPO is a structural vascular/overgrowth condition, non-drug care is the foundation of treatment and quality of life. [2]
Multidisciplinary specialist clinic – The child or adult is followed by a team (dermatology, vascular anomalies, genetics, surgery, physiotherapy, psychology). They create a single, long-term plan, avoid duplicated tests, and coordinate timing of procedures, which is crucial in rare PROS disorders like CLAPO. [1][2]
Regular monitoring and photography – High-quality photos and measurements of lip, face, neck, limbs, and body asymmetry at each visit help track progression and response to therapy (for example, to pulsed dye laser or sirolimus). This objective record is important because malformations change slowly over time. [1][2]
Skin care for capillary malformations – Gentle cleansers, fragrance-free moisturizers, and sun protection help avoid dryness, cracking, and bleeding of the lower-lip malformation. Good skin barriers reduce secondary infection risk and prepare the skin for procedures like laser. [1][3]
Infection prevention in lymphatic malformations – Lymphatic vesicles can leak or blister and are prone to cellulitis. Parents are taught early signs of infection, careful drying of skin folds, and when to seek antibiotics. Quick treatment lowers hospitalizations in people with complex lymphatic malformations. [2][3]
Compression garments or custom facial supports – For limbs or areas with venous/lymphatic swelling, properly fitted compression garments can reduce edema, heaviness, and pain. In children this must be done by experienced therapists to avoid harming growth plates or causing discomfort. [2][3]
Manual lymphatic drainage and physiotherapy – Specially trained physiotherapists use gentle massage and exercises to stimulate lymphatic drainage, maintain range of motion, and prevent muscle imbalance caused by asymmetry or overgrowth. This improves comfort and daily function. [2]
Occupational therapy and school adaptations – Occupational therapists help with fine-motor tasks, writing, feeding, or self-care if facial or limb overgrowth limits movement. They also advise schools about seating, extra time, or assistive devices so the child can participate fully. [1][2]
Psychological and social support – Visible facial or lip differences can cause bullying, anxiety, and low self-esteem. Psychologists and support groups help families talk about appearance, procedures, and uncertainty about the future, improving coping and adherence to treatment. [1][2]
Speech and feeding therapy – If lip, tongue, or jaw asymmetry affects speech clarity or swallowing, speech-language therapists can teach positioning, exercises, and safe feeding strategies. This may prevent aspiration and support language development. [1]
Dental and orthodontic care – Overgrowth and asymmetry can change jaw alignment and bite. Early and regular dental and orthodontic reviews help prevent caries, manage crowding, and plan any future corrective jaw or dental surgery in coordination with the vascular anomalies team. [1][2]
Customized oral appliances – In some patients, soft mouth guards or lip shields can protect fragile lower-lip capillary malformations from biting trauma or rubbing against teeth, reducing bleeding and ulceration during eating or sports. [3]
Pain-management strategies without drugs – Heat/cold packs, relaxation breathing, distraction, and pacing of activities can help manage chronic discomfort from swelling or heaviness, especially when families want to minimize long-term medicine use. [2]
Scar care after procedures – After laser, sclerotherapy, or surgery, careful wound care, silicone gels or sheets, and sun protection reduce hypertrophic scarring and pigment changes. This is important for visible areas like the lips and face. [3]
Healthy movement and exercise programs – Clinicians usually encourage regular age-appropriate physical activity, adapted as needed, to maintain cardiovascular fitness, joint mobility, and mental health. Over-protection can worsen deconditioning and pain. [2]
Weight management and nutrition counselling – Extra body weight can worsen venous and lymphatic congestion. Dietitians help families aim for balanced nutrition that supports growth without excessive weight gain, which is helpful in overgrowth syndromes. [2][3]
Genetic counselling and family education – Although CLAPO usually results from somatic (non-inherited) mutations, families often worry about recurrence and future pregnancies. Genetic counselling explains mosaicism, PROS, and evolving targeted therapies, helping with informed decisions. [1][4]
Support groups and rare-disease networks – Connecting with other families living with CLAPO/PROS through patient organizations reduces isolation, shares practical tips, and may offer information about clinical trials and expert centers. [1][2]
Education about trauma avoidance – Families learn to avoid unnecessary piercing, aggressive dental procedures, or trauma in areas with vascular malformations, because these can bleed heavily or heal poorly. Planning elective procedures in specialist centres is safer. [2][3]
Emergency action plan – The team often provides a written plan for emergency departments (what CLAPO is, medications, airway or bleeding risks, key specialists). Parents can carry this document so emergency staff act quickly and safely. [2]
Long-term follow-up and transition planning – As children with CLAPO grow, they need a planned transition from pediatric to adult services so complex treatments like sirolimus or alpelisib are not abruptly stopped and psychosocial support continues. [2][4]
Drug treatments
There is no single “CLAPO drug”. Most medicines target PROS/PIK3CA pathways or manage symptoms (pain, infection, thrombosis). Many uses are off-label and require an expert centre. [2][4]
I cannot realistically list 20 fully evidence-based drugs specific to CLAPO (the data just do not exist), but here are key medicines that appear in PROS and complex vascular malformation care.
Alpelisib (VIJOICE – PI3K inhibitor) – Alpelisib is an oral PI3Kα inhibitor and the first FDA-approved targeted drug for PROS, including severe PIK3CA-driven overgrowth and vascular anomalies. Adults often receive 250 mg once daily, while children ≥2 years start at 50 mg once daily, with dose adjustments per label. It slows abnormal overgrowth and can shrink lesions, but may cause high blood sugar, rash, diarrhea, and low blood counts, so close monitoring is essential. [1][2][4]
Sirolimus (Rapamune – mTOR inhibitor) – Sirolimus blocks the PI3K/AKT/mTOR pathway, which is over-active in many vascular malformations and PROS conditions. Studies show that oral sirolimus can reduce pain, swelling, bleeding, and complication rates in complex slow-flow malformations. Doses are weight-based (for example, ~0.8 mg/m² twice daily) and adjusted to target blood levels; side effects include immune suppression, mouth ulcers, high lipids, and infection risk, so it must be managed by experienced teams. [2][3] [5]
Topical or low-dose sirolimus – Some centres use topical sirolimus preparations on superficial capillary or lymphatic malformations to reduce redness and leakage while limiting systemic exposure. Evidence is still emerging, and formulations are usually prepared by hospital pharmacies. Monitoring is still needed, because systemic absorption can occur, especially on large areas. [3][5]
Propranolol oral solution (HEMANGEOL – β-blocker) – Propranolol is FDA-approved for proliferating infantile hemangioma, a vascular tumour, and sometimes considered when CLAPO overlaps with hemangioma-like components. Doses in infants start at about 0.6 mg/kg twice daily, titrated up under close monitoring. It constricts blood vessels and reduces abnormal vessel growth, but can cause low blood sugar, bradycardia, and bronchospasm, so careful selection and monitoring are required. [3][5]
Non-steroidal anti-inflammatory drugs (NSAIDs) – Medicines like ibuprofen are often used for mild to moderate pain or inflammatory flares around malformations. They inhibit cyclo-oxygenase enzymes and prostaglandin synthesis. While helpful for short-term pain, long-term or high-dose use can irritate the stomach or kidneys and must be avoided in patients with bleeding or kidney problems. [2]
Paracetamol (acetaminophen) – Paracetamol is a first-line pain reliever and fever reducer that does not affect platelets as much as NSAIDs. It is often preferred for routine pain and post-procedure discomfort in children with CLAPO. Overdose can damage the liver, so families must follow weight-based dosing exactly. [2]
Antibiotics for cellulitis or lymphangitis – People with lymphatic malformations may develop recurrent skin infections, which require prompt oral or intravenous antibiotics (for example, beta-lactams) chosen according to local guidelines and culture results. Rapid treatment reduces scarring and prevents sepsis or hospitalization. [2]
Short courses of systemic corticosteroids – In selected cases of severe inflammatory swelling or airway compromise, short bursts of systemic steroids (like prednisolone) may be used to reduce inflammation while other treatments (such as sirolimus or procedures) are arranged. Long-term steroid use is avoided due to growth suppression, metabolic effects, and infection risk. [2][3]
Antiplatelet agents (low-dose aspirin) – Some centres use low-dose aspirin in patients with venous malformations who are at risk of localized intravascular coagulopathy or thrombosis. Aspirin reduces platelet activation but increases bleeding risk, so the benefits and risks must be carefully weighed by a hematologist and vascular anomalies team. [2][3]
Anticoagulants (for thrombosis) – If patients develop deep-vein thrombosis or serious clotting within malformations, they may need anticoagulants (for example, low-molecular-weight heparin) under strict specialist supervision. This is not routine for all CLAPO patients but may be life-saving in selected cases. [2]
Topical corticosteroids – Mild topical steroid creams can be used briefly to calm eczema, irritation, or itching around capillary malformations or surgical scars. They modulate local inflammation but can thin the skin if overused, so they are used in short, supervised courses. [3]
Topical anesthetics – Creams containing lidocaine/prilocaine can reduce pain from injections, laser sessions, or minor procedures in sensitive lip or facial areas. They work by blocking nerve signals in the skin, but must be dosed carefully in infants to avoid systemic toxicity. [3]
Proton-pump inhibitors or gastro-protection – In patients receiving long-term sirolimus, corticosteroids, or NSAIDs, gastro-protective drugs may be used to reduce risk of ulcers or gastritis, especially if they already have GI symptoms. [2][5]
Antihistamines for itch and sleep – Non-sedating antihistamines can help with itching around lesions or allergic reactions to dressings, while sedating options may occasionally be used short-term at night when itching disturbs sleep. They block histamine receptors in the skin and brain. [3]
Oral iron or other hematinic supplements (when deficient) – If chronic bleeding or poor intake causes iron-deficiency anemia, oral iron or other hematinic supplements may be prescribed. These do not treat CLAPO itself but improve energy and exercise tolerance. [2]
Because evidence is limited, any targeted therapy (alpelisib, sirolimus) should ideally be given in or in close contact with a centre experienced in PROS clinical trials or registries. [2][4][5]
Dietary molecular supplements
No supplement can “cure” CLAPO, but some may support general health, wound healing, and immune function when used under medical supervision. Evidence is indirect and should be presented cautiously. [2]
Vitamin D – Adequate vitamin D supports bone health, muscle function, and immune regulation. Many children with chronic illnesses or limited outdoor activity are deficient. Doctors may recommend daily or weekly vitamin D doses based on blood levels, avoiding overdose which can cause high calcium and kidney problems. [2]
Omega-3 fatty acids (fish oil) – Omega-3s have mild anti-inflammatory effects and may support cardiovascular and metabolic health. If used, they are typically taken once or twice daily with food in age-appropriate doses. High doses can slightly increase bleeding tendency, so they should be coordinated with any antiplatelet or anticoagulant therapy. [3]
Vitamin C – Vitamin C is important for collagen synthesis and wound healing. Supplementation may be considered around surgical procedures or in children with poor intake of fruits and vegetables. Extremely high doses offer no proven CLAPO-specific benefit and can cause stomach upset or kidney stones. [3]
Zinc – Zinc supports skin repair and immune function. In children with recurrent infections or poor growth, clinicians may check zinc levels and give short-term supplements if low. Long-term excessive zinc can interfere with copper absorption and blood cell production. [2]
High-quality protein supplements – Where normal diet is insufficient, protein drinks or powders may support growth, wound healing, and postoperative recovery. A dietitian chooses formulations and doses to fit age, kidney function, and caloric needs. [2]
Probiotics – Some patients experience GI upset from systemic medicines such as sirolimus or antibiotics. Probiotics may help restore gut microbiota balance, although data are mixed. They should be used cautiously in severely immunosuppressed patients because of rare infection risk. [5]
Multivitamin tailored to age – For children with restricted diets, a simple age-appropriate multivitamin can reduce the risk of micronutrient gaps. Megadoses and “mega-antioxidant” formulas are not recommended, as they add cost and potential harm without CLAPO-specific evidence. [2]
Calcium (if needed) – In children on long-term steroids or with low dietary calcium, supplements may support bone health when combined with vitamin D and weight-bearing activity. Excessive calcium can cause constipation or kidney stones, so it must be dosed thoughtfully. [2]
Folate and B-complex – In patients with poor nutritional intake, B-vitamins support red-blood-cell production and energy metabolism. There is no direct evidence that they change CLAPO lesions, so they should not be marketed as “cures.” [2]
Medical nutrition formulas for feeding difficulties – When facial malformations or surgeries interfere with oral feeding, specialized high-calorie formulas (via bottle, cup, or tube) may help maintain growth until normal feeding is possible again. Dietitians select formulas and monitor weight closely. [1][2]
Immunity-booster and regenerative / stem-cell drugs
At present there are no approved stem-cell or regenerative drug therapies specifically for CLAPO. Claims of miracle stem-cell cures should be viewed with extreme caution. [2][4]
Vaccination and infection prevention – The most evidence-based “immunity booster” is simply staying up to date with routine vaccines (and any additional vaccines recommended for patients on immunosuppressants like sirolimus or alpelisib). This reduces serious infections that can complicate CLAPO care. [2][5]
Careful use of immunosuppressive targeted therapies – Drugs like sirolimus and alpelisib alter immune responses and tissue growth, but they are not classical “immune boosters”. Instead, the goal is to normalize over-active growth pathways while accepting some increased infection risk, monitored by blood tests and clinical review. [2][3][4]
No standard stem-cell therapy for CLAPO – Hematopoietic or mesenchymal stem-cell transplantation is not established for CLAPO or PROS and carries major risks. Any stem-cell proposal should be part of a regulated clinical trial with strong ethical oversight, not a commercial “miracle cure” offer. [2][4]
Nutritional and sleep optimisation – Adequate sleep, balanced diet, and exercise are still the safest ways to support immune function in children with CLAPO, especially if they take immunosuppressive drugs. Families should discuss any “immune-booster” supplements with their doctor to avoid interactions. [2]
Participation in regulated clinical trials – The most promising disease-modifying strategies (for example, newer PI3K or mTOR-pathway inhibitors) are being evaluated in clinical trials under careful safety monitoring. Joining such studies allows access to advanced care while generating evidence for future patients. [2][4][5]
Psychological resilience as “immune health” – Chronic stress can affect immune regulation. Psychosocial support, stress-management techniques, and supportive school environments may indirectly support immune and overall health by reducing chronic stress hormones. [2]
Surgical and interventional options
Surgery and interventional radiology are tailored to the individual pattern of malformations and overgrowth; they do not cure the underlying genetic mosaicism, but can improve function and appearance. [1][2]
Pulsed dye laser (PDL) for capillary malformation – PDL targets the red colour of capillary malformations in the lower lip and face. Case reports in CLAPO suggest it can safely reduce redness and thickness of the lip lesion, improving appearance and bleeding tendency, often over multiple sessions. [1][3] [4]
Sclerotherapy for lymphatic/venous malformations – Interventional radiologists inject sclerosing agents (such as bleomycin or ethanol-based solutions) into abnormal vessels to make them shrink. This is used to treat localized lymphatic or venous components causing pain, swelling, or cosmetic concern in CLAPO. [2][3]
Debulking or contouring surgery – Plastic or maxillofacial surgeons may remove or reshape overgrown soft tissue to reduce asymmetry, improve mouth closure, or relieve heaviness. Surgery is usually delayed until growth is more stable, and is planned together with vascular specialists to reduce bleeding and recurrence. [1][2]
Lymphatic malformation resection or drainage – For large cystic lymphatic malformations causing airway compression, feeding difficulties, or recurrent infection, partial resection or drainage procedures may be required, often combined with sclerotherapy or systemic therapy (for example, sirolimus) to limit regrowth. [2][3]
Orthognathic or orthodontic procedures – In adolescents or adults with major jaw asymmetry or malocclusion from overgrowth, combined orthodontic treatment and jaw surgery can improve bite, speech, and facial symmetry. This is complex planning that must consider vascular malformations to avoid excessive bleeding. [1][2]
Prevention
CLAPO is caused by somatic gene changes and cannot currently be prevented, but complications can often be reduced.
Early diagnosis and referral to a vascular anomalies/PROS centre. [1][2]
Education on infection signs in lymphatic lesions and rapid access to antibiotics. [2][3]
Good daily skin and oral care to prevent cracks, bleeding, and dental problems. [1][3]
Avoiding unnecessary trauma, piercings, or non-urgent surgery in affected areas. [2][3]
Maintaining healthy weight and physical activity to reduce venous/lymphatic congestion. [2]
Staying up to date with vaccinations, especially if on immunosuppressants. [2][5]
Regular follow-up with photography and measurements to detect changes early. [1][2]
Psychosocial support to prevent anxiety, depression, and school avoidance. [1]
Careful planning of pregnancy and delivery in adults with significant malformations. [2][4]
Considering participation in registries/clinical studies to access evolving standards of care. [2][4][5]
Each measure focuses on reducing infections, bleeding, thrombosis, functional limitations, and psychological impact, the main drivers of poor quality of life in vascular malformation syndromes. [2]
When to see doctors (and when it is urgent)
You should seek urgent medical care or emergency assessment if any of the following occur in a person with CLAPO: [1][2]
Sudden, rapidly increasing swelling of the face, tongue, or neck that affects breathing or swallowing. [1][2]
Heavy, uncontrolled bleeding from the lip or any malformation that does not stop with pressure. [2][3]
Signs of serious infection: high fever, redness spreading from a lesion, severe pain, or feeling very unwell. [2][3]
New neurological symptoms such as seizures, severe headache, or weakness, which might suggest associated brain involvement. [1][2]
You should also make a routine appointment with the CLAPO/PROS team when:
Pain, swelling, or functional problems (eating, speaking, walking) are slowly getting worse. [1][2]
School, work, or social life is affected by appearance, teasing, or low mood. [1]
You are considering pregnancy, major surgery, or long-distance travel. [2][4]
You have started or changed targeted medications and need regular blood tests. [2][4][5]
What to eat and what to avoid
There is no specific “CLAPO diet,” but nutrition can support overall health and reduce some risks.
Helpful to eat more often
A balanced, Mediterranean-style pattern with fruits, vegetables, whole grains, lean proteins, and healthy fats helps maintain healthy weight and cardiovascular health. [2]
Foods rich in vitamin C (citrus, berries, peppers) and protein (fish, eggs, beans) support tissue repair after procedures. [2][3]
Adequate fluid intake helps circulation and may reduce blood-viscosity-related symptoms. [2]
Calcium- and vitamin-D–rich foods (dairy or fortified alternatives) support bone health, especially if steroids are used. [2]
High-fibre foods support gut health, which can be affected by some medicines. [2][5]
Better to limit or avoid
Very salty processed foods, which can worsen fluid retention and swelling. [2]
Excessive sugary drinks and snacks that promote weight gain and metabolic problems, especially in patients on PI3K/mTOR pathway inhibitors (which can cause high blood sugar). [2][4]
Large amounts of alcohol in adults, which can interact with medications and worsen liver function. [2]
Unregulated “mega-dose” supplements or herbal products marketed as cures for vascular malformations or “stem-cell boosters,” due to lack of evidence and possible interactions. [2][4]
Smoking or vaping in older patients, which harms vascular and lung health and may complicate anesthesia and surgery. [2]
A dietitian familiar with chronic pediatric or rare-disease care can personalize these principles to each patient’s culture, preferences, and growth needs. [2]
Frequently asked questions (FAQs)
Is CLAPO syndrome cancer?
No. CLAPO is a vascular malformation and overgrowth condition, not a cancer. The abnormal tissue is generally benign, but it can cause serious problems by compressing structures or bleeding, so long-term specialist care is important. [1][2]Can CLAPO be cured completely?
At present, CLAPO cannot be completely cured because the underlying mosaic PIK3CA mutation remains. Treatments such as alpelisib, sirolimus, laser, and surgery can greatly improve symptoms and appearance, but ongoing follow-up is usually needed. [2][4][5]Is CLAPO inherited?
Most cases appear to be sporadic, caused by a somatic mutation that happens after conception, leading to mosaicism. The recurrence risk for future pregnancies is generally low, but genetic counselling is recommended to discuss uncertainties and evolving data. [1][4]How is CLAPO diagnosed?
Diagnosis is based on clinical features (lower-lip capillary malformation, facial/neck lymphatic malformations, asymmetry, overgrowth) and often confirmed by PIK3CA genetic testing on affected tissue. Imaging helps map malformations. [1][2]How is CLAPO different from other PROS conditions?
CLAPO shares PIK3CA mosaicism with other PROS disorders but is distinguished by its characteristic lower-lip capillary malformation and distribution of lymphatic/venous changes. Some experts view it as a recognizable phenotype within the broader PROS spectrum. [1][2][4]What is the role of alpelisib in CLAPO?
Because CLAPO is part of PIK3CA-related overgrowth spectrum, alpelisib can be considered in severe, systemic disease needing targeted therapy, following the FDA-approved PROS indication. The decision is highly individualized and should involve a PROS-experienced centre. [2][4][5]What is the role of sirolimus in CLAPO?
Sirolimus is widely used off-label in complex vascular malformations, including PROS-related lesions, to reduce pain, bleeding, and complications. It requires regular blood tests and infection monitoring but has improved quality of life in many patients with similar anomalies. [2][3][5]Will my child need many surgeries?
Not always. Some patients do well with medical therapy and limited procedures. Others may need staged interventions for airway issues, severe swelling, or asymmetry. The aim is to do the fewest necessary surgeries, at the safest time, coordinated by an expert team. [1][2][3]Can CLAPO affect the brain or other internal organs?
CLAPO mainly involves skin and superficial tissues, but because it is part of PROS, associated malformations in deeper tissues are possible. Doctors may order MRI or other imaging if there are neurological signs, seizures, or unusual symptoms. [1][2][4]Can children with CLAPO play sports and live a normal life?
Many children participate in school and sports with some adaptations (protective gear, avoiding high-impact trauma on affected areas). The goal of treatment is to maximize normal development and participation, not restrict it unnecessarily. [1][2]How often are follow-up visits needed?
In early childhood or when starting new targeted drugs, visits may be every 1–3 months. As the condition stabilizes, visits can often be spaced further apart, but annual specialist review usually remains important. [2][4]Are there special risks with anesthesia or surgery?
Yes. Vascular malformations in the airway or neck, and use of drugs like sirolimus, can change bleeding and infection risks. Surgery should be planned with anesthetists and surgeons familiar with vascular anomalies and PROS. [2][3][5]What about pregnancy in someone with CLAPO?
Pregnancy can worsen some vascular malformations because of hormonal and blood-volume changes. Women with CLAPO/PROS considering pregnancy should see a high-risk obstetrician and vascular anomaly team to adjust drugs (for example, stopping teratogenic agents like some targeted therapies) in advance. [2][4]Are there new treatments coming?
Yes. Research is ongoing into more selective PI3K/mTOR inhibitors, combination regimens, and refined interventional radiology techniques. Registries and clinical trials are gradually building evidence so that care becomes more standardized and effective. [2][4][5]Where can families find reliable information and support?
The best sources are vascular anomalies centres, clinical genetics departments, PROS/PIK3CA patient organizations, and peer-reviewed medical literature. Clinicians can help families identify trustworthy national and international groups rather than unregulated social-media advice. [1][2][4]
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 26, 2025.
