To summarize the clinical manifestation and genetic characteristics of Chinese patients with achondroplasia (ACH) which is caused by pathogenic variants fibroblast growth factor receptor 3 (FGFR3) gene and establish the reference value of height centiles and height for age growth curve of patients for a more practical, simple and useful growth evaluation tool in China.

Through a nationwide cross-sectional survey in China from July 2019 to January 2020 designed by Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 210 subjects (110 boys, 100 girls), who harbored the pathogenic variant of FGFR3 gene and were diagnosed with achondroplasia, were recruited. The clinical and genetic data of enrolled subjects were collected and analyzed to explore the clinical genetic characteristics of Chinese ACH patients. Furthermore, according to the data of height (body length under 2 years old) of boy and girl subjects aged 0-12 years, centiles and height for age growth curve of achondroplasia were calculated and established by LMS method respectively.

The characteristic clinical manifestations of 210 Chinese patients (0-14 years old) were disproportionate short stature (206/210, 98.1%), macrocephaly and characteristic facial features (205/210, 97.6%), trident configuration of the hands (191/210, 90.9%), limbs deformity (156/210, 74.3%), together with normal intelligence. Up to 81.9% (172/210) of patients have different complications, and the kyphosis (121/210, 57.6%) and narrow thoracic (79/210, 37.6%) are common complications. Besides, up to 98.6% (207/210) of patients harbored hotspot variants of FGFR3 gene which cause G380R amino acid substitutions. It is notable that the growth pattern of boy and girl patients (0-12 years old) is obviously different from the normal children (t=9.849, 9.596, P<0.01) respectively. The height different between ACH patients and normal children gradually widened with age. The average height of the boy (49.2 cm) and girl patients(48.4 cm) of achondroplasia at birth was -1.22 s and -2 s, however, at the age of twelve, the average height of the boy(113.7 cm) and girl patients(112.4 cm) of achondroplasia was -5.23 s and -6.15 s compared to currently standard reference height for age growth curve of normal children in China, respectively.

The results of our study demonstrated that in China disproportionate short stature, macrocephaly and characteristic facial features were typical manifestations of ACH patients, and that up to 98.6% of patients harbored hotspot variants of FGFR3 gene. In addition, the reference value of height centiles and height for age growth curve of ACH patients we establish will be a valuable tool for evaluating the growth pattern, monitoring factors affecting growth, estimating ultimate height, and assessing the curative effect of growth-promoting treatments in Chinese patients with achondroplasia.

Achondroplasia; Growth charts; Developmental disabilities; Dwarfism