Noonan Syndrome Growth Charts and Genotypes: 15-Year Longitudinal Single-Centre Study

Abstract

<b><i>Introduction:</i></b> Growth patterns in Noonan syndrome (NS) remain relatively unknown. The objective of this study was to provide growth reference curves for patients with NS and identify correlations between their growth, genotype, and clinical features. <b><i>Methods:</i></b> This was a 15-year-long, monocentric, observational, retrospective, non-interventional study. Children with NS followed up between 2005 and 2022 at “Bambino Gesù” Children’s Hospital, Italy, were included and excluded if they had received growth hormone treatment. Comparison of growth curves of participants with NS versus the general Italian population and further genotypic analyses were performed. <b><i>Results:</i></b> Overall, 190 eligible participants with NS were identified, with median (interquartile range) age of 14.01 (9.05–19.25) years (55.8% male). Cardiovascular anomalies were present in 85.3% of participants, most commonly pulmonary stenosis (52.6%) and atrial septal defects (36.8%); 48.1% of male participants had cryptorchidism. The most frequently detected mutations were in <i>PTPN11</i> (66.3%) and <i>SOS1</i> (13.9%). NS sex-specific centile curves for height, weight, body mass index, and height velocity were produced. For both sexes, the 50th percentile of height and weight for participants with NS overlapped with the 3rd percentile for the general Italian population. Both sexes with a <i>PTPN11</i> mutation had a significantly lower height and weight than those with “other mutations” at 5 years old. No significant associations were observed between cardiac anomalies and <i>PTPN11</i> mutation status. <b><i>Conclusion:</i></b> We present longitudinal data describing growth curves and trends, the natural history, and genotypes of the NS population, which provide a useful tool for clinicians in the management of NS.