Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature.
Mutations in RIT1, involved in the RAS-MAPK pathway, have recently been identified as a cause for Noonan syndrome. We present two patients with Noonan syndrome caused by a RIT1 mutation with novel phenotypic manifestations, severe bilateral lower limb lymphedema starting during puberty, and fetal hydrops resulting in intrauterine fetal death, respectively. Including our patients, a total of 52 patients have been reported with Noonan syndrome caused by a RIT1 mutation. Our report contributes to the delineation of the phenotype associated with RIT1 mutations and underlines that lymphatic involvement is part of this spectrum. In addition, we provide an overview of the currently described Noonan syndrome patients with RIT1 mutations in literature. © 2016 Wiley Periodicals, Inc.
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.|Department of Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
Doris
D
Milosavljević
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.|Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Eline
E
Overwater
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Saskia
S
Tamminga
Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.
Karin
K
de Boer
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Mariet W
MW
Elting
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Marion E
ME
van Hoorn
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Tuula
T
Rinne
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Arjan C
AC
Houweling
D005260:Female; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics* / Q000503:physiopathology; D035002:Lower Extremity / Q000503:physiopathology; D008297:Male; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D018631:ras Proteins / Q000235:genetics*
C486776:RIT1 protein, human; D018631:ras Proteins
Noonan syndrome; RASopathy; RIT1; hydrops fetalis; lymphedema