Parkes Weber syndrome

Revision as of 17:14, 5 April 2020 by Saud Khan (talk | contribs) (→‎Historical Perspective)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search

WikiDoc Resources for Parkes Weber syndrome

Articles

Most recent articles on Parkes Weber syndrome

Most cited articles on Parkes Weber syndrome

Review articles on Parkes Weber syndrome

Articles on Parkes Weber syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Parkes Weber syndrome

Images of Parkes Weber syndrome

Photos of Parkes Weber syndrome

Podcasts & MP3s on Parkes Weber syndrome

Videos on Parkes Weber syndrome

Evidence Based Medicine

Cochrane Collaboration on Parkes Weber syndrome

Bandolier on Parkes Weber syndrome

TRIP on Parkes Weber syndrome

Clinical Trials

Ongoing Trials on Parkes Weber syndrome at Clinical Trials.gov

Trial results on Parkes Weber syndrome

Clinical Trials on Parkes Weber syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Parkes Weber syndrome

NICE Guidance on Parkes Weber syndrome

NHS PRODIGY Guidance

FDA on Parkes Weber syndrome

CDC on Parkes Weber syndrome

Books

Books on Parkes Weber syndrome

News

Parkes Weber syndrome in the news

Be alerted to news on Parkes Weber syndrome

News trends on Parkes Weber syndrome

Commentary

Blogs on Parkes Weber syndrome

Definitions

Definitions of Parkes Weber syndrome

Patient Resources / Community

Patient resources on Parkes Weber syndrome

Discussion groups on Parkes Weber syndrome

Patient Handouts on Parkes Weber syndrome

Directions to Hospitals Treating Parkes Weber syndrome

Risk calculators and risk factors for Parkes Weber syndrome

Healthcare Provider Resources

Symptoms of Parkes Weber syndrome

Causes & Risk Factors for Parkes Weber syndrome

Diagnostic studies for Parkes Weber syndrome

Treatment of Parkes Weber syndrome

Continuing Medical Education (CME)

CME Programs on Parkes Weber syndrome

International

Parkes Weber syndrome en Espanol

Parkes Weber syndrome en Francais

Business

Parkes Weber syndrome in the Marketplace

Patents on Parkes Weber syndrome

Experimental / Informatics

List of terms related to Parkes Weber syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]


Overview

Parkes Weber Syndrome also known as (PKWS) is a rare vascular abnormality characterized by a cutaneous flush with underlying multiple CM (capillary malformation), VM (venuous malformation), LM (lymphatic malformation) and AVFs (arteriovenous fistulas), in association with soft tissue and skeletal hypertrophy of the affected limb. [1] [2][3][4] Discovered by Frederick P. Weber in 1907, who noted two patients with port-wine stains and enlargement of the limb with accompanying enlargement of the vasculature leading to a palpable thrill. Malformations can be present since birth, and in some cases are controlled by genetic mutations transferred in an autosomal dominant pattern. This disease is clinically distinct from Klippel-Trenaunay syndrome but the two are often confused as the presentation is very similar. AVMs present in PWS serve as the hallmark for distinguishing the two syndromes.[3][5]

Recently a disorder in the RASA1 gene has been implicated in development of this syndrome.[6] F. Parkes Weber's (1863-1962) name is also attached to hereditary hemorrhagic telangiectasia, Sturge-Weber syndrome, Weber-Christian disease, and Klippel-Trenaunay-Weber syndrome.

Historical Perspective

  • Parkes-Weber Syndrome was first discovered by Frederick Parkes Weber, an English dermatologist, in 1907.
  • In 2008, RASA1 mutations were first comfirmed in the pathogenesis of this syndrome, along with other fast-flow vascular syndromes.
  • There is no known cure for PWS, although symptomatic control is available in the form of embolization and corrective surgery depending on the implicit malformations.

Pathophysiology

Gene map locus is 5q13.1[7].

Six families reported by Eerola et al. in 2003, manifested atypical capillary malformations associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. They named this association CM-AVM for 'capillary malformation-arteriovenous malformation' and found mutation in the RASA1 gene in affected members of these families.

  • The pathogenesis is not well understood at this time, but theories have been put forward in literature:
    • Congenital blockage of deep veins draining the affected limb
    • Germ layer (mesodermal) irregularity leading to abnormal development of soft tissue and subsequent development of high flow AVMs.
    • RASA1 gene mutation has been associated with the development of PWS, involving the tyrosine kinase pathway. This gene is responsible for regulation of cellular growth and differentiation. It codes for the p120-RasGAP protein responsible for various growth factor receptors controlling stem cell migration and proliferation. In this disease the mutated gene codes for a non-functioning protein.
  • On gross pathology, capillary malformations, high flow arteriovenous fistulas, VMs and LMs are characteristic.

Clinical Features

PWS can present with:

  • Upper or lower limb hypertrophy. More commonly the lower limb is involved. Patients with AVFs (arteriovenuous fistula) have a greater degree of hypertrophy.
  • Bruit or thrill over the affected limb.
  • Abnormal bleeding/ recurrent bleeding from skin lesions
  • Large, flat, pink discolouration on the skin known as a port-wine stain (naevus flammeus)
  • Enlarged veins showing evidence of high flow AV shunting.
  • Capillary malformations resulting in petecheia on face, arms and legs
  • Telangiectasia
  • Venous malformations
  • Varicose veins
  • Congestive heart failure

Differentiating Parkes-Weber Syndrome from other Diseases

  • Parkes Weber Syndrome must be differentiated from other diseases that cause port-wine stains and capillary malformations, such as:
  • Klippel-Trenaunay Syndrome: KTS consists of the following triad of capillary malformation, venous malformation and lymphatic malformation. AVMs are present only in PWS.
  • Sturge-Weber syndrome: Sturge-Weber syndrome is characterized by a triad of facial port wine stains (classically the area of the ophthalmic and/or maxillary branch (segments V1/V2) of the trigeminal nerve), leptomeningeal angiomatosis, and ocular involvement. The capillary malformation associated with SWS usually presents as both upper and lower eyelid staining, and is often bilateral.[8]
  • Proteus syndrome — Proteus syndrome is an extremely rare disorder characterized by random overgrowth of body parts. The cause is considered to be mosaicism for a somatic activating mutation in the AKT1 oncogene.
  • CLOVES syndrome
  • Capillary malformation-arteriovenous malformation syndrome

Epidemiology and Demographics

  • Exact prevalence of PWS is unknown.[4]

Natural History, Complications and Prognosis

  • Early clinical features include
    • a capillary malformation resulting in pink, warm birthmarks flush with the skin called a port-wine stain
    • frequent or recurrent bleeding from malformations near the skin surface
    • cellulitis
    • varying degrees of hypertrophy of a limb (usually a leg)
    • pain in the affected limb which varies in severity
    • increased blood flow through an arteriovenous malformation leading to cardiac issues
  • If left untreated, patients with PWS progress to fatal high output heart failure, or excessive bleeding can be cause of death. Other complications include cutaneous ischemia, cardiac hypertrophy and limb amputation.[7]
  • Prognosis is generally fair. As PWS is a progressive condition, management depends on the extent of the overgrowth and the problems it causes. Any comorbidities, the condition of the patient's heart, refractory nature of the disease, overall health of the patient influence outcomes along with timely diagnosis and intervention. Overgrowth is progressive until epiphyseal closure.

Diagnosis

  • Diagnosis of PWS is a difficult process and is frequently misdiagnosed as KTS. It is made on clinical grounds. A combination of cutaneous capillary-Lymphatic-venuous malformations along with arterio-venous malformations as the main defect define the syndrome.

Imaging Findings

  • Imaging modalities useful to diagnose and map vascular malformations include:
      • Magnetic resonance imaging (MRI): This is a high-resolution scan employed to gauge the extent of the hypertrophy (overgrowth) of tissue and provides insight to the problems due to it. Subsequently, MR projection angiography may be used to distinguish PWS from KTS noninvasively.
      • Ultrasound (also called ultrasonography): An ultrasound helps to visualise vascular system abnormalities and can determine the blood flow through the AVM. Antenatal testing can sometimes allude to malformations.
      • Computerized tomography scan (also called a CT or CAT scan): A CT scan shows detailed images of the area in slices and is especially helpful for evaluating the bones in the affected limb.
      • Angiogram: A dye is injected which outlines the vasculature, providing a detailed view of the blood vessels in the affected limb. This is the gold standard to visualise the location and degree of AVMs. Digital Subtraction Angiography can be used to differentiate between high and low flow AVMs. This technique is used mostly for patients who are candidates for embolization therapy.
      • Echocardiogram: To check the condition of the patients heart.


Treatment

Medical Therapy

  • There is no treatment for PWS; the mainstay of therapy is supportive care. Depending on the extent of malformations, embolization can be done to block off AVMs and to prevent overgrowth of limbs.
  • The use of compressive stockings can prevent edema and minimize discomfort.[7]

Surgery

  • Embolization in conjunction with removal of AVMs is the most common approach to the treatment of PWS.[9]
  • A recent case report suggests early amputation of the limb as having better outcomes than placing stents in high flow AVMs.[10]

Prevention

  • PWS is a genetic disease as such there are no primary preventive measures available.


Multi Sliced CT

See Also

References

  1. Eerola, I.; Boon, L. M.; Mulliken, J. B.; Burrows, P. E.; Dompmartin, A.; Watanabe, S.; Vanwijck, R.; Vikkula, M. Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am. J. Hum. Genet. 73: 1240-1249, 2003. PMID 14639529
  2. Mulliken, J. B.; Young, A. E. (eds.): Vascular Birthmarks: Hemangiomas and Vascular Malformations. Philadelphia: W. B. Saunders Co., 1988
  3. 3.0 3.1 Lee BB. (2012). "Klippel-Trenaunay Syndrome: is this term still worthy to use?". Acta Phlebol. 13: 1–2.
  4. 4.0 4.1 "Genetics home reference".
  5. Gloviczki, P (2009). "Vascular malformations: an update". Perspectives in vascular surgery and endovascular therapy.
  6. N, Revencu (2008). "Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations". Hum mutat. 29: 959–965.
  7. 7.0 7.1 7.2 SZELIGA, Adrianna (September 2019). "Parkes Weber Syndrome". Journal of Health, education and sport.
  8. Tallman, B (1991). "Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications". Pediatrics.
  9. Banzic, I (2017 July). "Parkes Weber syndrome—Diagnostic and management paradigms: A systematic review". Phlebology. Check date values in: |date= (help)
  10. Acar, Zeydin. "Short- and mid-term effects of covered stent implantation on extremity findings and heart failure in Parkes Weber syndrome: a case report". European Heart Journal - Case Reports.


Template:WikiDoc Sources