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Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature
Author(s) -
Milosavljević Doris,
Overwater Eline,
Tamminga Saskia,
de Boer Karin,
Elting Mariet W.,
van Hoorn Marion E.,
Rinne Tuula,
Houweling Arjan C.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37657
Subject(s) - noonan syndrome , phenotype , medicine , mutation , genetics , biology , gene
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.