Longitudinal Outcomes in Noonan Syndrome.

Purpose: Noonan syndrome and related disorders (NS) are multisystemic conditions affecting approximately 1:1000 individuals. Previous natural history studies were conducted prior to widespread comprehensive genetic testing. This study provides updated longitudinal natural history data in participants with molecularly confirmed NS.

Methods: Comprehensive medical, developmental, and healthcare utilization (HCU) data were abstracted from the medical record of participants with molecularly confirmed NS. Primary outcomes included developmental outcomes, classroom setting, and HCU.

Results: 172 patients with molecularly confirmed NS were followed for 1,142.2 patient-years total. An average of 3.7 affected organ systems on initial evaluation. Sitting, walking, and talking in two-word phrases all occurred earlier than in previous cohorts (p=0.003, p=0.001, p<0.0001 respectively). Genotype influenced age at milestones and classroom setting; feeding difficulties also influenced age at milestones. HCU was significantly higher in patients with NS compared to peers (p<0.0001) and highest in infancy and adolescence.

Conclusion: Developmental outcomes have improved compared to previous cohorts. Predictors of outcome may identify those at highest risk for developmental delay allowing for appropriate intervention. Children and adolescents with NS have an increased burden of HCU compared to their peers. Multidisciplinary care coordination is needed to decrease medical burden and improve health for patients and families.