Parkes Weber syndrome

Parkes Weber syndrome is a rare congenital condition characterized by a large number of abnormal blood vessels. The vascular system consists of arteries, which carry oxygen-rich blood from the heart to the body’s various organs and tissues; veins, which carry blood back to the heart; and capillaries, which are tiny blood vessels that connect arteries and veins. Parkes Weber syndrome is characterized by vascular abnormalities known as capillary malformations and arteriovenous fistulas, which are present from birth. The capillary malformations increase blood flow near the surface of the skin. They usually look like large, flat, pink stains on the skin, and because of their color are sometimes called “port-wine stains.” In people with Parkes Weber syndrome, capillary malformations occur together with multiple micro-arteriovenous fistulas, which are tiny abnormal connections between arteries and veins that affect blood circulation. These arteriovenous fistulas can be associated with life-threatening complications including abnormal bleeding and heart failure.

Another characteristic feature of Parkes Weber syndrome is overgrowth of one limb, most commonly a leg. Abnormal growth occurs in bones and soft tissues, making one of the limbs longer and larger around than the corresponding one.

Some vascular abnormalities seen in Parkes Weber syndrome are similar to those that occur in a condition called capillary malformation-arteriovenous malformation syndrome ¹. Capillary malformation-arteriovenous malformation syndrome and some cases of Parkes Weber syndrome have the same genetic cause.

Parkes Weber syndrome is a rare condition; its exact prevalence is unknown ².

Parkes Weber syndrome is similar to the more common Klippel-Trenaunay syndrome and is treated in much the same way. Parkes Weber syndrome management typically depends on the presence and severity of symptoms and may include embolization or surgery in the affected limb ¹.

Parkes Weber syndrome causes

Some cases of Parkes Weber syndrome result from mutations in the RASA1 gene. When the condition is caused by RASA1 gene mutations, affected individuals usually have multiple capillary malformations. People with Parkes Weber syndrome who do not have multiple capillary malformations are unlikely to have mutations in the RASA1 gene; in these cases, the cause of the condition is often unknown.

The RASA1 gene provides instructions for making a protein known as p120-RasGAP, which is involved in transmitting chemical signals from outside the cell to the nucleus. These signals help control several important cell functions, including the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), and cell movement. The role of the p120-RasGAP protein is not fully understood, although it appears to be essential for the normal development of the vascular system.

Mutations in the RASA1 gene lead to the production of a nonfunctional version of the p120-RasGAP protein. A loss of this protein’s activity disrupts tightly regulated chemical signaling during development. However, it is unclear how these changes lead to the specific vascular abnormalities and limb overgrowth seen in people with Parkes Weber syndrome.

Parkes Weber syndrome inheritance pattern

Most cases of Parkes Weber syndrome occur in people with no history of the condition in their family. These cases are described as sporadic.

When Parkes Weber syndrome is caused by mutations in the RASA1 gene, it is sometimes inherited from an affected parent. In these cases, the condition has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.

Parkes Weber syndrome symptoms

Parkes Weber syndrome affects different children in different ways. One child may have a mild form with a small capillary malformation and one hand or foot slightly larger than the other. Another child may have a capillary malformation that runs from her chest down her leg, lots of swelling, heart problems and one limb that is much larger than the other.

Some possible symptoms of Parkes Weber syndrome include:

• Birthmarks caused by capillary malformations on the skin; they increase blood flow near the surface of the skin and usually look like large, flat, pink stains on the skin, and because of their color are sometimes called “port-wine stains.”
• Frequent or recurrent bleeding, from abnormal capillaries near the surface of the skin.
• Cellulitis (infections in the skin)
• Hypertrophy (excessive growth) of the bone and soft tissue of the affected limb (which may lead to a difference in size between the affected and non-affected limb), usually a leg.
• Multiple arteriovenous fistulas due to abnormal connections between arteries and veins. These arteriovenous fistulas can be associated with life-threatening complications including abnormal bleeding and heart failure.

Parkes Weber syndrome main signs and symptoms typically include a capillary malformation on the skin; hypertrophy (excessive growth) of the bone and soft tissue of the affected limb; and multiple arteriovenous fistulas (abnormal connections between arteries and veins) which can potentially lead to heart failure. There also may be pain in the affected limb and a difference in size between the limbs ³. Some cases of Parkes Weber syndrome result from mutations in the RASA1 gene, and are inherited in an autosomal dominant manner. In these cases, affected people usually have multiple capillary malformations. People with Parkes Weber syndrome without multiple capillary malformations are unlikely to have mutations in the RASA1 gene; in these cases, the cause of the condition is often unknown.

Parkes Weber syndrome diagnosis

Doctors can sometimes see evidence of Parkes Weber syndrome in a prenatal ultrasound, and the capillary malformation (“port-wine stain”) is almost always apparent when your child is born.

If a child is older and you believe he has Parkes Weber syndrome, the first step to making a diagnosis is a complete medical history and a thorough physical exam. In many cases, that initial exam gives us enough information to diagnose Parkes Weber syndrome.

If there’s any doubt, your doctor may recommend one or more of the following imaging tests, which can help determine the correct diagnosis and the appropriate next steps in treatment:

• Magnetic resonance imaging (MRI): This high-resolution scan shows the extent of the hypertrophy (overgrowth) of tissue and gives your doctor information about what problems it may be causing.
• Ultrasound also called ultrasonography: An ultrasound helps your doctor see your child’s vascular system to examine abnormalities and determine how much blood is flowing through the arteriovenous malformation.
• Computerized tomography scan also called a CT or CAT scan: A CT scan shows detailed images of the area affected by Parkes Weber syndrome and is especially helpful for evaluating the bones in the affected limb.
• Angiogram: In this study, an interventional radiologist injects a dye into your child’s blood vessels, giving doctors a detailed view of the blood vessels in the affected limb.
• Echocardiogram: An echocardiogram allows your child’s doctor to check the condition of her heart.

After your doctor complete all necessary tests, a team of vascular anomalies specialists will review and discuss what they have learned about your child’s condition. Then they will meet with you and your family to discuss the results and outline the best treatment options for your child.

Parkes Weber syndrome treatment

There is no cure currently exists for Parkes Weber syndrome. Treatment depends on the symptoms and usually involves several specialists, such as interventional radiologist, neurosurgeons, vascular surgeons, cardiologists and dermatologists. Heart problems should be treated by a cardiologist. The arteriovenous malformations (AVMs) and/or arteriovenous fistulas are treated with surgery or with embolization. Leg differences are treated by an orthopedist. Capillary malformations can be treated by a dermatologist when the patients are concerned with the cosmetic appearance.

Supportive care may include compression garments (tight-fitting pieces of clothing on the affected limb to reduce pain and swelling); these may also protect the limb from bumps and scrapes, which can cause bleeding and are also recommended in cases of lymphedema. Heel inserts may be used if the legs are different lengths, which can aid in walking normally. Various pain medications and antibiotic medications may be prescribed as needed.

Surgical care

Surgeons can perform what’s called a debulking procedure, during which abnormal vessels and some of the overgrown tissue are removed.

Orthopedic surgery

If Parkes Weber syndrome affects the foot or leg, sometimes the limb can become excessively large. Should that be the case, your doctor may recommend an operation. For instance, an orthopedic surgeon can reshape your child’s foot if it cannot fit into a shoe.

Epiphysiodesis

Sometimes in Parkes Weber syndrome one leg grows longer than the other. Orthopedic surgeons can estimate how long a child’s leg will be when she is fully-grown. If it appears the difference will be more than an inch they may recommend a procedure called epiphysiodesis. This procedure, which is usually done when a child is between 10 and 14 years old, interrupts the leg’s growth plate and stops the leg from growing when it’s reached a certain length

Other treatments for Parkes Weber syndrome

Embolization

A specialist called an interventional radiologist can inject a substance that eliminates the abnormal connections between your child’s arteries and veins.

Laser therapy

Laser treatments can help lighten your child’s capillary malformation, and speed healing if your child’s lesion begins to bleed.

Other specialists that care for patients with Parkes Weber syndrome

Depending on your child’s symptoms and the progression of the disease, we may also bring in:

• Physical therapists — Parkes Weber syndrome can affect your child’s arm or leg, making it hard or painful for your child to move it. A physical therapist can help ease the pain and increase your child’s range of movement.
• Occupational therapists — Children with Parkes Weber syndrome sometimes get behind on developing motor skills because of physical problems related to the disease. An occupational therapist can get your child back on track.
• Counselors — As your child gets older, he or she may be uncomfortable with the capillary malformation on his or her skin. One of our counselors can help your child deal with the psychological and social issues related to having a birthmark.

Parkes Weber syndrome prognosis

Parkes Weber syndrome is a progressive condition, which means that it will grow as your child grows. The long-term outlook depends on a few factors:

• the extent of the disease
• the amount of hypertrophy (overgrowth) in your child’s limb or limbs
• the condition of your child’s heart
• the abnormal blood vessels’ response to therapy
• the overall health of your child
• your child’s tolerance of specific medications, procedures or therapies
• new developments in treatment

Depending on the severity of your child’s Parkes Weber syndrome, your doctor may recommend a series of follow-up visits to check for complications and making sure that Parkes Weber syndrome is managed effectively.

References

1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. 2011 Feb 22 [Updated 2019 Sep 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK52764
2. Parkes Weber syndrome. https://ghr.nlm.nih.gov/condition/parkes-weber-syndrome
3. Parkes Weber Syndrome. http://www.childrenshospital.org/conditions-and-treatments/conditions/p/parkes-weber-syndrome