Genotype-phenotype correlation analysis in Japanese patients with Noonan syndrome

Yasuko Shoji, Shinobu Ida, Tetsuya Niihori, Yoko Aoki, Nobuhiko Okamoto, Yuri Etani, Masanobu Kawai

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12 Citations (Scopus)


Noonan syndrome (NS) is a heterogeneous disorder with multiple congenital malformations. Recent advances in molecular and genetic approaches have identified a number of responsible genes for NS, most of which are components of the RAS/MAPK signaling pathway, and genotype-phenotype correlation analyses have been extensively performed; however, analysis of Japanese NS patients is limited. Here, we evaluated clinical characteristics in genetically diagnosed NS patients and their relationships to genotypes. A total of 48 clinically diagnosed NS were included, and responsible mutations were identified in 39 patients (81.3%) with PTPN11 mutations being the most prevalent followed by SOS1 mutations. Cardiac anomalies including pulmonary stenosis and hypertrophic cardiomyopathy were most prevalent (87.2%), and the prevalence of hypertrophic cardiomyopathy was greater in patients without PTPN11 mutations than in those with PTPN11 mutations. Short stature was the second-most prevalent (69.2%) characteristic, and present height SD score was significantly associated with height SD score at 1 year old. Patients with SOS1 mutations had greater present height SD score and better growth during infancy. These findings suggest the presence of a genotype-phenotype correlation in Japanese patients with NS, which enables us to use genetic information to predict the clinical course and may allow for genotype-based medical interventions.

Original languageEnglish
Pages (from-to)983-994
Number of pages12
JournalEndocrine Journal
Issue number11
Publication statusPublished - 2019


  • Cardiac anomaly
  • Noonan syndrome
  • PTPN11
  • Short stature


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