title: The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome.
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.
authors.affiliation: SW Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Joyce
authors.affiliation: Department of Dermatology, St George's Hospital NHS Trust, London, UK.
authors.forename: Kristiana
authors.initials: K
authors.lastname: Gordon
authors.affiliation: SW Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
authors.forename: Glen
authors.initials: G
authors.lastname: Brice
authors.affiliation: Lymphovascular Research Unit, Cardiovascular & Cell Sciences Research Institute, St George's University of London, London, UK.
authors.forename: Pia
authors.identifier: http://orcid.org/0000-0002-2190-1356
authors.initials: P
authors.lastname: Ostergaard
authors.affiliation: Department of Gastroenterology, St George's Healthcare NHS Trust, London, UK.
authors.forename: Rani
authors.initials: R
authors.lastname: Nagaraja
authors.affiliation: SW Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Short
authors.affiliation: SW Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moore
authors.affiliation: Lymphovascular Research Unit, Cardiovascular & Cell Sciences Research Institute, St George's University of London, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Mortimer
authors.affiliation: SW Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.|Lymphovascular Research Unit, Cardiovascular & Cell Sciences Research Institute, St George's University of London, London, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004476:Ectodermal Dysplasia / Q000175:diagnosis*; D019066:Facies; D005183:Failure to Thrive / Q000175:diagnosis*; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis*; D006801:Humans; D008208:Lymphatic System / Q000000981:diagnostic imaging*; D061305:Lymphoscintigraphy; D008297:Male; D009634:Noonan Syndrome / Q000175:diagnosis*; D010641:Phenotype