Objective To analyze the clinical phenotype and genetic characteristics of children with Noonan syndrome (NS), in order to provide theoretical evidence for early diagnosis and treatment of the disease. Methods A retrospective analysis of the clinical data and genetic testing results of 21 NS children diagnosed from January 2016 to January 2023 were performed. Therapeutic follow-up results of some of the shorter children were also included. Therapeutic follow-up results of some of the shorter children were also included. Results Among the 21 NS patients, there were 13 males and 8 females, with a diagnosis age ranging from 5 days to 14 years old and a mean age of 4.6 years old. Most common clinical features included special facial features (n=12), congenital heart disease (n=11), short stature (n=9), feeding difficulties (n=6), abnormal skeletal development (n=3), hearing disorder (n=3), and sparse hair (n=3). In addition to classic phenotypes, rare phenotypes such as sparse teeth, scoliosis, photophobia, hair follicle keratosis, epilepsy, and arrhythmias were also observed. Seven mutant genes were identified by genetic testing, including PTPN11(n=7), BRAF(n=4), LZTR1(n=3), SOS1(n=3), KRAS(n=2), RAF1(n=1), and SHOC2(n=1). Nine short stature children were treated with rhGH for an average of 16.6 months, with a mean height change from -3.62s to -3.21s. Conclusions Complete exome sequencing is helpful for early diagnosis of NS patients. In addition to the classic phenotype of NS, the RAF1 gene may be associated with frequent atrial arrhythmias, suggesting a new phenotype spectrum. Heterozygous variants in the LZTR1 gene may result in a mild phenotype with sparse hair, which is a rare phenotype of RAF1 and SHOC2 variants of NS. The short-term efficacy of rhGH treatment in NS patients is acceptable, but the correlation between rhGH efficacy and genotype was not clear.
Key words
Noonan syndrome /
gene /
phenotype /
growth hormone
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