J Pediatr Genet 2018; 07(04): 158-163
DOI: 10.1055/s-0038-1653977
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Co-occurrence of Noonan and Cardiofaciocutaneous Syndrome Features in a Patient with KRAS Variant

Fernando Rodríguez
1  School of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile
,
Carla Vallejos
1  School of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile
,
Víctor M. Bolanos-Garcia
2  Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom
,
Diana Ponce
1  School of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile
,
Nancy Unanue
1  School of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile
,
Francisco Garay
3  División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
,
Fernando Cassorla
1  School of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile
,
Mariana Aracena
3  División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
4  Unidad de Genética, Hospital Dr. Luis Calvo Mackenna, Santiago, Chile
› Author Affiliations
Funding This work was supported by Fondecyt Grant 1140450 to F.R.
Further Information

Publication History

15 January 2018

09 April 2018

Publication Date:
16 May 2018 (online)

Abstract

We report the case of a 3-year-old girl, who is the third child of nonconsanguineous parents, with short stature, hypertrophic cardiomyopathy, and mild dysmorphic features; all suggestive of Noonan syndrome. In addition, the patient presents with feeding difficulties, deep palmar and plantar creases, sparse hair, and delayed psychomotor and language development, all characteristics frequently observed in cardiofaciocutaneous syndrome. Molecular analysis of the Ras/ MAPK pathway genes using high-resolution melting curve analysis and gene sequencing revealed a de novo KRAS amino acid substitution of leucine to tryptophan at codon 53 (p.L53W). This substitution was recently described in an Iranian patient with Noonan syndrome. The findings described in this report expand the phenotypic heterogeneity observed in RASopathy patients harboring a KRAS substitution, and advocate for the inclusion of genes with low mutational frequency in genetic screening protocols for Noonan syndrome and other RASopathies.

Note

Written informed consent was obtained from the patient's mother for publication of this case report and accompanying images.


Supplementary Material