DermNet provides Google Translate, a free machine translation service. Note that this may not provide an exact translation in all languages

Klippel–Trénaunay syndrome

Author: Vladimir Popa-Nimigean, Medical Student, School of Clinical Medicine, University of Cambridge, Cambridge, UK. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell/Maria McGivern. October 2018.


Klippel–Trénaunay syndrome — codes and concepts
open

What is Klippel–Trénaunay syndrome?

Klippel–Trénaunay syndrome (KTS) is a rare congenital vascular bone syndrome that is characterised by a triad of symptoms and features; these being:

The syndrome is also called Klippel–Trénaunay–Weber syndrome, angio-osteohypertrophy syndrome, and haemangiectactic hypertrophy.

Klippel–Trénaunay syndrome

Who gets Klippel–Trénaunay syndrome?

Klippel–Trénaunay syndrome is a rare disease, affecting one in 20,000–40,000 children. It affects both sexes equally and it occurs in all races [1]. While it mostly occurs sporadically, some inherited cases have been reported [3].

What causes Klippel–Trénaunay syndrome?

While the exact cause of Klippel–Trénaunay syndrome is not clear, several genes and pathways have been identified in its pathogenesis. Notably, PIK3CA gene mutations have been detected in some cases of Klippel–Trénaunay syndrome. PIK3CA encodes for a subunit of the phosphoinositide 3-kinase enzyme, which is involved in cell proliferation and migration. Gain-of-function mutations can lead to tissue hypertrophy in the bone, soft tissue, and blood vessels [2,4].

The angiogenic gene VG5Q has also been implicated in Klippel–Trénaunay syndrome [5].

What are the clinical features of Klippel–Trénaunay syndrome?

Capillary vascular naevus

One or more capillary vascular malformations (port-wine stains) are present in the overwhelming majority of patients with Klippel-Trénaunay syndrome and this is usually the first noticeable feature [1,2,6]. Commonly, the capillary malformation occurs over the affected hypertrophic limb, but it can also be present at other sites. Rarely, the affected area can blister and bleed [2].

Venous malformations

Varicose veins are a common feature of Klippel–Trénaunay syndrome. They tend to be larger than normal varicose veins and they can be painful. Varicose veins may not be present initially. They usually become noticeable in later infancy, childhood, or adolescence. Deep veins can also be affected, increasing the risk of developing deep vein thrombosis (DVT) [1–3,6].

Additionally, the formation of veins may be atypical, resulting in lateral veins or persistent sciatic veins (inflammation in the veins leading from the spine down to the legs), for example. Bleeding can also occur, which may result in bleeding from the rectum or blood in the urine [6–9].

Malformations in Klippel-Trénaunay syndrome are of slow-flow vessels, and fast-flow arteriovenous malformations (clumps of blood vessels that link between arteries and veins) are not present. Bruits (murmurs caused by the narrowing of arteries) tend to be absent on examination [8].

Limb hypertrophy

Limb hypertrophy affects the lower limb in most cases (about 95%), with the remainder affecting the upper limb. Limb enlargement is disproportionate, with the width of the leg enlarging more than length, as the skin and muscles tend to become thicker than other sites. The average difference in limb length is around 2 cm. The length discrepancy can cause uneven walking, unstable gait, or pain. The child might appear to have scoliosis [1–3,6,9].

Less commonly, syndactyly or polydactyly (extra fingers or toes) may occur.

What are the complications of Klippel–Trénaunay syndrome?

The possible complications of Klippel-Trénaunay syndrome include [1,2]:

How is Klippel–Trénaunay syndrome diagnosed?

The diagnosis of Klippel–Trénaunay syndrome is made clinically when the classical triad of port-wine stain, varicose veins, and limb hypertrophy are present. While a diagnosis of Klippel-Trénaunay syndrome can be suspected in a newborn when a port-wine stain is present, the confirmation comes later when other symptoms become more apparent [1–3].

Possible diagnostic tests include:

  • Magnetic resonance imaging
  • Magnetic resonance angiography
  • Computed tomography (CT) or CT venography
  • Colour duplex ultrasonography
  • Ultrasound during pregnancy [3,10].

What is the differential diagnosis for Klippel–Trénaunay syndrome?

Conditions that can be mistaken for Klippel–Trénaunay syndrome include:

  • Parkes Weber syndrome — this is characterised by fast-flow arteriovenous malformations and fistulae [8]
  • Proteus syndrome — in which there are usually no obvious deformities/features at birth; Proteus syndrome presents later with progressive and more generalised musculoskeletal deformities [11].
  • Macrodystrophia lipomatosa — in this form of limb hypertrophy, there is an absence of soft-tissue vascular malformations and a lack of limb-length discrepancy [12].

What is the treatment for Klippel–Trénaunay syndrome?

There is no specific cure for Klippel–Trénaunay syndrome, and generally, most patients can be managed conservatively. Specific treatments and procedures can also be used to reduce symptoms and prevent complications [1,6,10].

Conservative management

Compression stockings are often used to control the symptoms of varicose veins, alleviate pain and swelling, and prevent complications such as bleeding (in which case dressings, leg elevation, and rest are recommended [1,10].

If the difference in leg lengths is small (< 2 cm), shoe raisers might be recommended to allow the child to walk more easily and prevent compensatory scoliosis. Physiotherapy can also help reduce swelling in the affected limb [1,10].

Ligation and stripping

Ligation of the veins (the surgical tying off of veins) can be used to treat varicose veins in conjunction with vein stripping. (See DermNet NZ's page of Leg vein therapies). This treatment is not advised in children [1,7,10].

Sclerotherapy

Sclerotherapy refers to the injection of a sclerosing agent into the veins in order to collapse them. It is used to treat complications arising from varicose veins so they are no longer noticeable on the surface of the skin. It can be used in children after detailed scans of the veins in the leg have been made. Several sclerotherapy sessions months apart are usually required [1,7,10].

A variation of this procedure is foam sclerotherapy, which involves injecting a foaming agent (in addition to the sclerosing one) into the veins [7].

Laser therapy

Laser therapy can be used to treat or manage the port-wine stains, although to a limited extent. It is also used to treat small varicose veins and as an adjuvant for sclerotherapy or endovascular ablation (see below) [7,10].

Endovascular thermal ablation

Problematic varicose veins can be closed off by using high-frequency radio waves to create local heat in the affected vein. This is generally associated with fewer risks and faster recovery compared to ligation and stripping [7].

Epiphysiodesis

If the asymmetry between the affected and unaffected legs is larger than 2 cm, epiphysiodesis can be performed to slow down the growth in the affected leg. This procedure involves prematurely fusing the growth plate of a bone and needs to be timed correctly in order to match the lengths of the legs by the end of the growth phase [6,7].

Alternatively, the normal leg can also be lengthened surgically to achieve matching size [1].

What is the outcome for Klippel–Trénaunay syndrome?

Patients with Klippel–Trénaunay syndrome tend to do very well. While it is not a life-threatening condition and most patients end up having normal lives, ongoing care is required. This is best provided by a multidisciplinary team of dermatologists, vascular and orthopaedic surgeons, and general surgeons [1,10]. Some people may require counselling to adjust to the cosmetic aspects of the disease [3].

See smartphone apps to check your skin.
[Sponsored content]

 

Related information

 

References

  1. Birthmark Unit, Great Ormond Street Hospital for Children. Klippel-Trenaunay syndrome. Reviewed July 2015. Available at: www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/klippel-trenaunay-syndrome (accessed 27 September 2018).
  2. National Institutes of Health US National Library of Medicine. Klippel-Trenaunay syndrome. Reviewed July 2018. Available at: https://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome (accessed 27 September 2018)
  3. Edens AC. Klippel-Trenaunay syndrome. Medline Plus. Reviewed October 2017. Available at: https://medlineplus.gov/ency/article/000150.htm (accessed 27 September 2018).
  4. Vahidnezhad H, Youssefian L, Uitto J. Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). Exp Dermatol 2016; 25: 17–9. DOI: 10.1111/exd.12826. PubMed
  5. Tian XL, Kadaba R, You SA, et al. Identification of an angiogenic factor that when mutated causes susceptibility to Klippel–Trénaunay syndrome. Nature 2004; 427: 640–5. DOI: 10.1038/nature02320. Journal
  6. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P. Klippel-Trénaunay syndrome: spectrum and management. Mayo Clin Proc 1998; 73: 28–36. DOI: 10.1016/S0025-6196(11)63615-X. PubMed
  7. Cleveland Clinic, Klippel-Trenaunay syndrome (KTS). Reviewed January 2016. Available at: https://my.clevelandclinic.org/health/diseases/17152-klippel-trenaunay-syndrome-kts (accessed 27 September 2018).
  8. Mendiratta V, Koranne RV, Sardana K, Hemal U, Solanki RS. Klippel Trenaunay Parkes-Weber syndrome. Indian J Dermatol Venereol Leprol 2004; 70: 119–22. PubMed
  9. Cohen MM. Klippel-Trenaunay syndrome. Am J Med Genet 2000; 93: 171–5. Journal
  10. Kihiczak GG, Meine JG, Schwartz RA, Janniger CK. Klippel–Trenaunay syndrome: a multisystem disorder possibly resulting from a pathogenic gene for vascular and tissue overgrowth. Int J Dermatol 2006; 45: 883–90. DOI: 10.1111/j.1365-4632.2006.02940.x. PubMed
  11. El-Sobky TA, Elsayed SM, EL Mikkawy DME. Orthopaedic manifestations of Proteus syndrome in a child with literature update. Bone Rep 2015; 3: 104–8. DOI: 10.1016/j.bonr.2015.09.004. PubMed Central
  12. Abdulhady H, El-Sobky T, Elsayed N, Sakr H. Clinical and imaging features of pedal macrodystrophia lipomatosa in two children with differential diagnosis review. J Musculoskelet Surg Res 2018; 2(3): 130–4. DOI: 10.4103/jmsr.jmsr_8_18. Journal

On DermNet NZ

Other websites

Books about skin diseases

See the DermNet NZ bookstore.