Growth patterns of patients with Noonan syndrome: correlation with age and genotype. Issue 5 (May 2016) - Cessans, Catie
Abstract : Background: Growth patterns of patients with Noonan syndrome (NS) were established before the involved genes were identified. Objective: The goal of this study was to compare growth parameters according to genotype in patients with NS. Subjects and methods: The study population included 420 patients (176 females and 244 males) harboring mutations in the PTPN11, SOS1, RAF1, or KRAS genes. NS-associated PTPN11 mutations ( NS-PTPN11 ) and NS with multiple lentigines-associated PTPN11 mutations ( NSML-PTPN11 ) were distinguished. Birth measures and height and body mass index (BMI) measures at 2, 5, 10 years, and adulthood were compared with the general population and between genotypes. Results: Patients with NS were shorter at birth (mean birth length standard deviation score (SDS): –1.0 ± 1.4; P < 0.001) and throughout childhood than the healthy population, with height SDS being –2.1 ± 1.3 at 2 years, and –2.1 ± 1.2 at 5 and 10 years and adulthood ( P < 0.001). At birth, patients with NS-PTPN11 were significantly shorter and thinner than patients with NSML-PTPN11, SOS1, or KRAS . Growth retardation was significantly less severe and less frequent at 2 years in patients with NSML-PTPN11 and SOS1 than in patients with NS-PTPN11 ( P < 0.001 and P = 0.002 respectively). Patients with NS had lower BMI at 10 years ( P < 0.001). No difference between genotypes was demonstrated. Conclusion: Determining the growth patterns of patients with NS according to genotype should better inform clinicians about the natural course of growth in NS so that they can optimize the follow-up and management of these patients.