Lymphatic Malformations in Parkes Weber's Syndrome: Retrospective Review of 16 Cases in a Vascular Anomalies Center

Abstract

Introduction Parkes Weber's syndrome (PWS) is a rare genetic disorder characterized by overgrowth and vascular malformations, primarily affecting the extremities. While PWS is known to be associated with arteriovenous and capillary malformations, the potential involvement of lymphatic malformations (LMs) has not been previously reported. The objective of this study is to investigate the presence of lymphatic anomalies in PWS patients and their role in the development of limb asymmetry.

Materials and Methods This is a retrospective study of patients diagnosed with PWS in a Vascular Anomalies Center from 1994 to 2020. Clinical data were obtained from medical records including diagnostic imaging, lymphoscintigraphy, and genetic testing. The Institutional Review Board and Ethics Committee have approved this study.

Results A total of 16 patients aged 18 interquartile range 14.7 years diagnosed with PWS were included (50% female). Six of the 16 patients with PWS had clinical and imaging data suggestive of LM (37.5%) and 3 of them had genetic variants in RASA1 (2/3) or KRAS (1/3). Limb asymmetry was greater in patients with isolated PWS (2.6 ± 0.8 cm) than in the PWS-lymphatic anomalies population (2 ± 0.7 cm), although not significant (p = 0.247). One in 6 patients with PWS-LM required amputation (16.6%) versus 1 in 10 in isolated PWS (10%).

Conclusion Lymphatic anomalies may be present in a significant number of patients with PWS and could have a role in limb asymmetry and outcomes. It is paramount to investigate their existence and distinguish them from true overgrowth.

Keywords

Parkes Weber's syndrome - lymphatic malformation - arteriovenous malformation - vascular malformations

Publikationsverlauf

Eingereicht: 06. Mai 2023

Angenommen: 15. August 2023

Accepted Manuscript online:
18. August 2023

Artikel online veröffentlicht:
29. September 2023

• References

• 1 Banzic I, Brankovic M, Maksimović Ž, Davidović L, Marković M, Rančić Z. Parkes Weber syndrome-diagnostic and management paradigms: a systematic review. Phlebology 2017; 32 (06) 371-383
• 2 Limaye N, Boon LM, Vikkula M. From germline towards somatic mutations in the pathophysiology of vascular anomalies. Hum Mol Genet 2009; 18 (R1): R65-R74
• 3 Boon LM, Mulliken JB, Vikkula M. RASA1: variable phenotype with capillary and arteriovenous malformations. Curr Opin Genet Dev 2005; 15 (03) 265-269
• 4 Revencu N, Boon LM, Mulliken JB. et al. Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations. Hum Mutat 2008; 29 (07) 959-965
• 5 Larralde M, Abad ME, Luna PC, Hoffner MV. Capillary malformation-arteriovenous malformation: a clinical review of 45 patients. Int J Dermatol 2014; 53 (04) 458-461
• 6 Macmurdo CF, Wooderchak-Donahue W, Bayrak-Toydemir P. et al. RASA1 somatic mutation and variable expressivity in capillary malformation/arteriovenous malformation (CM/AVM) syndrome. Am J Med Genet A 2016; 170 (06) 1450-1454
• 7 de Wijn RS, Oduber CE, Breugem CC, Alders M, Hennekam RC, van der Horst CM. Phenotypic variability in a family with capillary malformations caused by a mutation in the RASA1 gene. Eur J Med Genet 2012; 55 (03) 191-195
• 8 ISSVA Classification of Vascular Anomalies ©2018 International Society for the Study of Vascular Anomalies. Accessed May 4, 2023, at: issva.org/classification
• 9 Lu Q, Xu J, Liu N. Chronic lower extremity lymphedema: a comparative study of high-resolution interstitial MR lymphangiography and heavily T2-weighted MRI. Eur J Radiol 2010; 73 (02) 365-373
• 10 von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg 2014; 12 (12) 1495-1499
• 11 Moreno Alfonso JC, López Gutiérrez JC, Triana Junco PE, San Basilio Berenguer M. Capillary malformation of the lower lip: CLAPO syndrome. An Pediatr (Engl Ed) 2023; 98 (04) 321-322
• 12 Moreno Alfonso JC, Pérez Martínez A, Molina Caballero AY, Bardají Pascual C. Respiratory distress syndrome due to pulmonary hypoplasia and neonatal congenital lymphedema. An Pediatr (Engl Ed) 2023; 98 (04) 323-324
• 13 Wang X, Guo L, Zhang B. et al. Haploinsufficiencies of FOXF1, FOXC2 and FOXL1 genes originated from deleted 16q24.1q24.2 fragment related with alveolar capillary dysplasia with misalignment of pulmonary veins and lymphedema-distichiasis syndrome: relationship to phenotype. Mol Cytogenet 2022; 15 (01) 48
• 14 Hong T, Yan Y, Li J. et al. High prevalence of KRAS/BRAF somatic mutations in brain and spinal cord arteriovenous malformations. Brain 2019; 142 (01) 23-34
• 15 Sevick-Muraca EM, King PD. Lymphatic vessel abnormalities arising from disorders of Ras signal transduction. Trends Cardiovasc Med 2014; 24 (03) 121-127
• 16 Burrows PE, Gonzalez-Garay ML, Rasmussen JC. et al. Lymphatic abnormalities are associated with RASA1 gene mutations in mouse and man. Proc Natl Acad Sci U S A 2013; 110 (21) 8621-8626
• 17 Chen D, Teng JM, North PE, Lapinski PE, King PD. RASA1-dependent cellular export of collagen IV controls blood and lymphatic vascular development. J Clin Invest 2019; 129 (09) 3545-3561