Abstract
The RASopathies, which include Noonan syndrome (NS) and Cardiofaciocutaneous syndrome (CFC), are autosomal dominant disorders with genetic heterogeneity associated with germline mutations of genes in the Ras/mitogen-activated protein kinase (MAPK; RAS–MAP kinase) pathway. The conditions overlap and are characterised by facial dysmorphism, short stature and congenital heart disease. NS and CFC, in particular, are known to be associated with lymphatic problems, but this has not been well characterised to date. We describe 11 patients with Noonan or CFC syndrome with significant, persistent and progressive lymphatic dysplasia. The lymphatic disorders in Noonan and CFC syndrome are rare, but have a characteristic pattern with bilateral lower limb lymphoedema, genital swelling with chylous reflux and frequent systemic involvement, including intestinal lymphangiectasia and chylothoraces, which may be progressive. Lymphoscintigraphy demonstrates reflux and/or rerouting of lymphatic drainage associated with incompetent veins on the venous duplex scans.
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We thank all the patients who took part in this study and the Noonan Syndrome Association who sponsored this study.
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Joyce, S., Gordon, K., Brice, G. et al. The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. Eur J Hum Genet 24, 690–696 (2016). https://doi.org/10.1038/ejhg.2015.175
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DOI: https://doi.org/10.1038/ejhg.2015.175
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