Phenotypic Characterization and recombinant human growth hormone Therapeutic Response in ACAN Children With Short Stature: A Real-World Study.

OBJECTIVE

To investigate deep phenotypes and evaluate the efficacy of recombinant human growth hormone (rhGH) therapy in children with growth retardation carrying heterozygous ACAN variants.

METHODS

We retrospectively analyzed 37 children with heterozygous ACAN variants identified among 1528 individuals with growth retardation at a tertiary pediatric medical center in China between January 2017 and April 2024. Deep phenotyping and follow-up were conducted.

RESULTS

Among the 37 children, 78.4% had short stature, and 75.7% exhibited advanced bone age. Thirty-three distinct heterozygous ACAN variants were identified, including 19 novel variants. In the treatment group (n = 17), rhGH therapy lasted 4-61 months. Growth velocity at 3, 6, 9, 12, and 18 months was significantly higher than baseline (all P < .05). Changes in height standard deviation score at 18 and 24 months were significantly greater than those at 3 and 6 months (all P < .05). In the untreated group (n = 13), follow-up lasted 3-58 months, with final growth velocity of 0-6.98 cm/y.

CONCLUSION

Short stature and advanced bone age are common features of individuals with ACAN variants and represent strong indications for ACAN genetic screening. rhGH therapy demonstrates a growth-promoting effect in these children.