Introduction: Noonan syndrome (NS) is a relative frequent genetic disorder, mainly characterized by dysmorphic face features, congenital heart defects and short stature. Though delayed pubertal development has been described in both sexes, the physiopathological root remains unclear. This study aims at characterizing puberty development in Noonan syndrome.
Materials and Methods: The study population included 111 individuals with a molecular diagnosis of NS. Data on puberty development was retrospectively collected from medical records. The sample was torn into two groups according to the presence or absence of delayed puberty. The correlation between age of puberty onset or occurrence of delayed puberty with sex, genotype, use of recombinant growth hormone (rhGH), cryptorchidism, heart disease, height, body mass index (BMI), IGF-1 levels, and bone age before puberty was assessed.
Results: Delayed puberty was found in 25% patients with similar frequency in boys and girls. The table below summarizes features analyzed in each group. Height SDS before puberty were significantly lower on delayed puberty group. Besides, adult height was similar in both groups. No correlation was found between sex, genotype, use of rhGH, cryptorchidism, heart disease, BMI SDS, IGF-1 levels, and pubertal delay or age at start of puberty.
|Delayed Puberty||Normal Puberty||P-values|
|Sex (F:M)||14 : 14||44 : 55||0.759|
|Pathogenic variant in PTPN11||16 (57%)||71 (71%)||0.217|
|Use of rhGH||15 (54%)||36 (36%)||0.155|
|Age at the start of puberty (y)|
|Male||15.1 ± 1.0||11.7 ± 1.0||<0.001|
|Female||14.2 ± 1.4||11.1 ± 1.3||<0.001|
|Age of evaluation before puberty onset (y)||8.7 ± 0.5||8.9 ± 0.5||0.129|
|Height-SDS before puberty onset||-3.4 ± 1.6||-2.3 ± 0.9||0.003|
|BMI SDS before puberty onset||-0.5 ± 1.1||-0.3 ± 1.0||0.294|
|IGF1-SDS before puberty onset||-1.3 ± 1.4||-0.3 ± 1.2||0.090|
|Bone age delay before puberty onset||-2.0 ± 1.5||-1.4 ± 1.4||0.088|
|Time to complete puberty (T2 to T5) (y)||3.4 ± 2.1 (n = 10)||3.9 ± 1.8 (n = 30)||0.268|
|Adult Height SDS||-2.3 ± 1.1 (n = 20)||-2.0 ± 0.9 (n = 38)||0.179|
Conclusion: Delayed puberty is frequently observed in children with NS and resembles constitutional delay of growth and puberty seen in children with idiopathic short stature. The lack of correspondence between genotype and pubertal delay may show that this feature is linked to the RAS/MAPK signal transduction pathway in a general way.
22 Sep 2021 - 26 Sep 2021