METHODS: Children who met the FSS diagnostic criteria and had informed consent were included in the study. The trio whole-exome sequencing method (trio-WES) was used to detect and evaluate the NPR2 variants.
RESULTS: A total of 16 children with short stature were included in this study (pretreatment height ≤ -2 standard deviation (SD) in both the patient and the shorter parent, unknown genetic etiology). NPR2 variants were identified in 12.5%(2/16) of the participants. Patient A was a 6-year-old male and 103.7 cm tall (-3.11SD), while Patient B was a 9-year-old female and 123.2 cm tall (-1.88SD). However, their heights increased after recombinant human growth hormone (rhGH) treatment. The height of patient A increased by 0.36SD six months after treatment while that of patient B increased by 1.22SD after one and a half years of treatment.
CONCLUSIONS: NPR2 variant causes FSS. The growth rate of children significantly improved after rhGH treatment. However, further follow-up study is needed to determine the final height after long-term treatment.