Title
Noonan syndrome in diverse populations
Date Issued
01 September 2017
Access level
open access
Resource Type
journal article
Author(s)
Kruszka P.
Porras A.R.
Addissie Y.A.
Moresco A.
Medrano S.
Mok G.T.K.
Leung G.K.C.
Tekendo-Ngongang C.
Uwineza A.
Thong M.K.
Muthukumarasamy P.
Honey E.
Ekure E.N.
Sokunbi O.J.
Kalu N.
Jones K.L.
Kaplan J.D.
Abdul-Rahman O.A.
Vincent L.M.
Love A.
Belhassan K.
Ouldim K.
El Bouchikhi I.
Shukla A.
Girisha K.M.
Patil S.J.
Sirisena N.D.
Dissanayake V.H.W.
Paththinige C.S.
Mishra R.
Klein-Zighelboim E.
Chávez Pastor M.
Skinner S.A.
Prijoles E.J.
Badoe E.
Gill A.D.
Shotelersuk V.
Smpokou P.
Kisling M.S.
Ferreira C.R.
Mutesa L.
Megarbane A.
Kline A.D.
Kimball A.
Okello E.
Lwabi P.
Aliku T.
Tenywa E.
Boonchooduang N.
Tanpaiboon P.
Richieri-Costa A.
Wonkam A.
Chung B.H.Y.
Stevenson R.E.
Summar M.
Mandal K.
Phadke S.R.
Obregon M.G.
Linguraru M.G.
Muenke M.
Publisher(s)
Wiley-Liss Inc.
Abstract
Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.
Start page
2323
End page
2334
Volume
173
Issue
9
Language
English
OCDE Knowledge area
Genética, Herencia
Subjects
Scopus EID
2-s2.0-85026314237
PubMed ID
Source
American Journal of Medical Genetics, Part A
ISSN of the container
15524825
Sponsor(s)
We are grateful to the individuals and their families who participated in our study. P.K., Y.A.A, and M.M. are supported by the Division of Intramural Research at the National Human Genome Research Institute, NIH. We thank the Chulalongkorn Academic Advancement into its 2nd Century Project. Partial funding of this project was from a philanthropic gift from the Government of Abu Dhabi to the Children's National Health System. We would like to acknowledge GeneDx and Dr. Benjamin Solomon for providing molecular testing for NS free of charge.
Sources of information:
Directorio de Producción Científica
Scopus