Abstract:

Objective: To analyze the clinical features and genetic changes of 3 children in short stature with ACAN gene mutation. Methods: The clinical data, laboratory examinations, and genetic testing results of 3 children with ACAN gene mutations diagnosed with short stature at our pediatric endocrine disease clinic from 2018 to 2020 were collected, and the literature was reviewed for analysis and summary. Results: All the three children had a short family history, and their clinical manifestations were short stature. One patient had a slight limitation of the flexion activity of the thoracolumbar spine, and no other system abnormalities were found. Among them, the oldest of the 3 children was 5 years and 1 month, and the bone age was roughly consistent with or slightly advanced than the actual age, and the peak growth hormone challenge in 2 cases was less than 10 μg/L. The variations in the ACAN gene are c.G1877A and c.7360, respectively_ 7361del and c.7038_ 7039insCGGTGT, case 1 and case 2 are novel mutations that have not been reported in major databases. After the application of recombinant human growth hormone, the height of all three children improved. Reviewing the literature at home and abroad, we found that there were 120 children and 216 relatives reported at present. Among them, there were 80 ACAN gene variants related to short stature registered in HGMD, of which short stature was the most important clinical manifestation, followed by skeletal dysplasia. Conclusions: Mutations of ACAN gene mainly lead to short stature and skeletal dysplasia in children, and their clinical bone phenotypes are diverse, which can also only be manifested as short stature. For children with short stature, especially those with short stature family history, no matter whether they have skeletal abnormalities, they should be alert to this gene mutation.

Key words: ACAN gene, Short stature, Idiopathic short stature