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

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Growth patterns in Noonan syndrome (NS) are not well-established.
• Understanding NS growth is crucial for clinical management and patient care.

Purpose of the Study:

• To develop growth reference curves for pediatric patients with Noonan syndrome.
• To investigate correlations between NS growth, genetic mutations, and clinical phenotypes.

Main Methods:

• A 15-year retrospective, observational study of 190 children with NS (excluding those on growth hormone treatment).
• Development of sex-specific centile curves for height, weight, BMI, and height velocity.
• Genotypic analysis to identify common mutations (PTPN11, SOS1) and correlate with growth parameters.

Main Results:

• Noonan syndrome growth curves show significantly reduced height and weight compared to the general Italian population (50th percentile aligns with 3rd percentile).
• Patients with PTPN11 mutations exhibited lower height and weight at age 5 compared to those with other mutations.
• High prevalence of cardiovascular anomalies (85.3%) and cryptorchidism in males (48.1%) noted; no association found between cardiac anomalies and PTPN11 status.

Conclusions:

• The study provides the first longitudinal growth data and reference curves for Noonan syndrome patients.
• These growth curves serve as a valuable clinical tool for managing NS, aiding in monitoring and intervention.
• Genotype-phenotype correlations highlight the impact of specific mutations, like PTPN11, on growth trajectories in NS.