To explore the clinical and genetic characteristics of Noonan syndrome (NS), and to evaluate the efficacy and safety of recombinant human growth hormone (rhGH) in treatment of children with NS.

Five patients with NS (patients 1-5) diagnosed at the First Affiliated Hospital of Bengbu Medical University from January 2021 to February 2023 were selected as research subjects. Among them, patients 1-4 were children with NS, and patients 3 and 4 were siblings. Patient 5 was the mother of patients 3 and 4. Due to slow growth of elder brother (patient 3), brothers (patients 3 and 4) and his mother (patient 5) underwent family genetic testing in the Department of Pediatric Endocrinology of our hospital, and no other relevant examinations were performed on patient 4 and 5. Patients 1-3 and patient 5 underwent high-throughput sequencing, and the results were verified by Sanger sequencing. Patient 4 only underwent Sanger sequencing. Clinical data of patients 1-5 were analyzed by retrospective research method, including clinical manifestations, examination results at admission, genetic test results, treatment and follow-up outcomes. The procedures followed in this study complied with the regulations of the Ethics Review Committee of the First Affiliated Hospital of Bengbu Medical University, and was approved by the committee (Approval No. 2023YJS141), and informed consent was obtained from all patients or their guardians.

The analysis results of patients 1-5 were as follows. ①History taking and physical examination results: 4 cases (patients 1-4) were male, and 1 case (patient 5) was female. Four cases (patients 1-4) had NS typical facial features, while 1 case (patient 5) had no obvious special facial features. Four cases (patients 1-3 and 5) were complicated with congenital heart disease (CHD), of which patient 1 was complicated with pulmonary artery stenosis, patient 2 was complicated with patent ductus arteriosus and ventricular septal defect, patient 3 was complicated with pulmonary artery stenosis and atrial septal defect, and patient 5 was complicated with atrial septal defect. Patients 1-3 had short stature. Patient 5 had didelphia and iron-deficiency anemia. ②Laboratory and imaging test results of patients 1-3: the levels of insulin and insulin-like growth factor (IGF)-1 of patient 3 were < 2 mIU/L and < 25 ng/mL, respectively, which both were lower than the normal values, while the other laboratory test results of patients 1-3 were all normal. MRI of the hypothalamus and pituitary gland for patient 3 suggested a left temporal arachnoid cyst, and patient 2 had mild scoliosis, while the other imaging test results of patients 1-3 were all normal. ③Genetic testing results: patient 1 had a likely pathogenic variant of the LZTR1 gene c. 851G>A(p.R284H) inherited from his father. Patient 2 had a pathogenic variant of the LZTR1 gene c. 1943-256C>T with both parents being wild-type. Patients 3-5 all had a pathogenic variant of the SOS1 gene c. 1654A>G(p.R552G). In patients 3 and 4, this variant was inherited from their mother (patient 5), while the origin of this variant in patient 5 was unknown. ④Treatment and follow-up results: two patients (patients 1 and 3) were treated with recombinant human growth hormone (rhGH), and showed an increased growth rate and height standard deviation (s) compared to pre-treatment, and with significantly elevated IGF-1 levels. No significant abnormalities in thyroid function were observed. No clinical symptoms such as scoliosis, headache, or joint pain appeared. Patient 3 experienced temporary impairment of fasting blood glucose.

NS can affect multiple systems throughout the body, with the main clinical manifestations being typical facial features, heart defects, and short stature. The heterogeneity of clinical manifestations is significant, making it prone to misdiagnosis and missed diagnosis in clinical settings. Clinicians should be vigilant to the possibility of NS for children with typical facial features, short stature, heart diseases, or other organ lesions. For NS children with short stature, treatment with rhGH can significantly improve their height.