Última actualización:
6/6/2023
Años publicados: 1987, 1990, 1998, 2000, 2002, 2008, 2012, 2015, 2018, 2023
NORD gratefully acknowledges John B. Mulliken, MD, Co-Director, Vascular Anomalies Center, Director, Craniofacial Center, Boston Children’s Hospital, for assistance in the preparation of this report.
Summary
Klippel-Trenaunay syndrome (KTS) is a rare vascular disorder that is present at birth (congenital) and characterized by three features: cutaneous capillary malformation (“port-wine stain”), lymphatic anomalies and abnormal veins in association with variable overgrowth of soft tissue and bone. KTS occurs most frequently in the lower limb and less commonly in the upper extremity.
Introduction
The eponym KTS generated controversy in the medical literature since the first report of the condition in the early 20th century. The French physicians, Klippel and Trenaunay, described patients with capillary stains (improperly called “hemangiomas” at that time), venous varicosities and overgrowth. In the same era, the English dermatologist, Parkes Weber, reported the combination of “hemangiomas” and overgrowth of a limb. For many years, the names of all three physicians were linked as a confusing (and incorrect) term “Klippel-Weber-Trenaunay syndrome,” which unfortunately is sometimes used to this day.
Since the latter 20th century, it is well-recognized that Parkes Weber and Klippel-Trenaunay syndromes are entirely different. Parkes Weber syndrome consists of fast-flow, multiple microscopic arteriovenous connections with variable capillary staining of an enlarged limb (usually the lower extremity). In contrast, KTS is a slow flow combined vascular disorder involving abnormal capillaries (C), lymphatics (L) and veins (V). Therefore, many investigators use the abbreviation CLVM, rather than KTS, and restrict the designation for patients who have all three anomalous vascular components. Other authors apply the KTS term more broadly and include patients with only capillary stain (CM) or combined capillary and venous anomalies (CVM) in the lower limb in the absence of lymphatic abnormalities. Now that genetic testing is available, it is possible to more precisely diagnose patients with these various combinations of vascular anomalies.
Capillary Malformation (CM)
At birth, KTS presents with scattered, geographic capillary stains. With age, the surface of the CM becomes studded with tiny lymphatic vesicles that often ooze clear fluid and turn black due to intralesional bleeding.
Lymphatic Malformation (LM)
LM presents as localized or generalized overgrowth caused by micro- and macrocystic anomalies, sometimes in association with lymphedema. Often there is lymphatic swelling and fatty deposition on the opposite foot. The lymphatic anomalies can also occur in the pelvis, bladder and lower gastrointestinal tract. Lymphatic cysts in the spleen are also common. LM is documented by ultrasonography and/or MRI. Lymphography shows that lymphedema is the result of diminished number or absence of lymphatic channels.
Episodic infections (cellulitis) are common and probably related to poor lymphatic drainage in the limb.
Venous Malformation (VM)
Venous abnormalities are always present but variable and involve the entire affected extremity. Typically, there are anomalous embryonic veins called the “marginal system.” Dilatation of superficial veins may not be apparent in infancy but becomes more prominent with age. LM and VM can also involve the pelvic or abdominal organs resulting in bleeding from the rectum, vagina or urinary bladder. Abnormal fatty deposits accompany the venous and lymphatic anomalies.
Many patients with extensive abnormal veins have a low-grade hematologic condition called “localized intravascular coagulopathy” (LIC), this can be determined by measuring increased D-dimers in the blood. Stagnant blood in the dilated veins may clot and trigger a generalized bleeding disorder called “disseminated intravascular coagulopathy” (DIC).
Overgrowth
Enlargement of the limb can be minimal to extremely distorted. Overgrowth in length often occurs; however, in some patients the affected limb is shorter than normal. Frequently there is enlargement of the opposite foot.
KTS is caused by a change (variant or mutation) in the PIK3CA gene. This mutation does not occur in the germ cells (egg and sperm) but only in the body cells after fertilization. Therefore, KTS is not an inherited condition and is not passed on in a family.
Klippel-Trenaunay syndrome is a rare disorder affecting males and females in equal numbers. The disorder occurs worldwide.
KTS is diagnosed based on physical signs and symptoms. Computed axial tomography (CAT) and magnetic resonance imaging (MRI) scans, and color doppler studies may be useful in determining the extent of the condition and how best to manage it.
Treatment
Recommended management for the following malformations associated with KTS:
Capillary Malformation
The vesicles in the CM can be improved by laser therapy, sclerotherapy or sometimes
resection and closure of the skin or replacement with a split-thickness skin graft.
Lymphatic Malformation
Macrocystic LM can be deflated by sclerotherapy (injection of irritating solutions). Microcystic LM is less responsive to sclerotherapy and may require resection.
Venous Malformation
Blood stagnates in large, dilated veins, and thus there is a risk for initiating a clotting disorder or thrombosis and pulmonary embolism. Anticoagulation with heparin (subcutaneously injected) is often necessary prior to radiologic or surgical intervention. Conversion to a direct oral anticoagulant (DOAC) may be considered. Large venous channels can be obliterated by sclerotherapy or endovascular laser. Chronic bleeding from the colon may require surgical resection. Bleeding lesions in the bladder can be controlled by laser through a cystoscope. An elastic compressive stocking is useful to minimize discomfort and swelling due to venous distension in the limb.
Overgrowth
Enlarged toes may require amputation to narrow the foot and permit footwear. Discrepancy in leg length can be corrected by inserting a lift in the shoe on the normal foot to prevent compensatory curvature of the spine (scoliosis). Surgical closure of the growth plate at the knee (epiphysiodesis) is often needed to equalize leg length.
Staged contour resection is possible to diminish girth of the limb. These procedures are less effective if the abnormal fat and vasculature extends beneath the deep fascia of the leg into the muscle layer.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Contact for additional information about Klippel-Trenaunay syndrome:
Vascular Anomalies Center (VAC)
Boston Children’s Hospital
300 Longwood Avenue
Boston, MA 02115
Tel: 617-355-5226
Email: [email protected]
Website: https://www.childrenshospital.org/vac
Clinical Practice Guidelines for Klippel-Trenaunay Syndrome (KTS)
https://k-t.org/assets/images/content/BCH-Klippel-Trenaunay-Syndrome-Management-Guidelines-1-6-2016.pdf Updated 1/6/2016. Accessed April 27, 2023.
TEXTBOOKS
Mulliken JB, Burrows PE, Fishman SJ (eds). Mulliken and Young’s Vascular Anomalies: Hemangiomas and Malformations. 2nd edition. New York: Oxford University Press. 2013.
JOURNAL ARTICLES
Luks VL, Kamitaki N, Vivero MP, et al. Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. J Pediatr. 2015 Apr;166(4):1048-54.e1-5. doi: 10.1016/j.jpeds.2014.12.069. Epub 2015 Feb 11. https://www.ncbi.nlm.nih.gov/pubmed/25681199
INTERNET
Klippel-Trenaunay syndrome. MedlinePlus. May 17, 2021. Klippel-Trenaunay syndrome: MedlinePlus Genetics. Accessed April 27, 2023
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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