Phenotypic Characterization and rhGH Therapeutic Response in ACAN Children with Short Stature: A Real-World Study
Su Wu1, Yiyun Cui1, Yunchong Chen1
1Department of Endocrinology, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China.
Insights
Children with ACAN variants often have short stature and advanced bone age. Recombinant human growth hormone (rhGH) therapy effectively promotes growth in these pediatric patients.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Growth Disorders
Background:
- Heterozygous variants in the ACAN gene are associated with growth retardation.
- Deep phenotyping is crucial for understanding the clinical manifestations of genetic growth disorders.
Purpose of the Study:
- To investigate the deep phenotypes of children with growth retardation carrying heterozygous ACAN variants.
- To evaluate the efficacy of recombinant human growth hormone (rhGH) therapy in this cohort.
Main Methods:
- Retrospective analysis of 37 children with heterozygous ACAN variants identified from 1,528 individuals with growth retardation.
- Deep phenotyping and follow-up assessments were conducted.
- Comparison of growth parameters between rhGH-treated and untreated groups.
Main Results:
- Short stature (78.4%) and advanced bone age (75.7%) were prevalent findings.
- 33 distinct heterozygous ACAN variants, including 19 novel ones, were identified.
- rhGH therapy significantly increased growth velocity and height standard deviation score compared to baseline and in the untreated group.
Conclusions:
- Short stature and advanced bone age are key indicators for ACAN genetic screening in children.
- rhGH therapy demonstrates a significant growth-promoting effect in children with heterozygous ACAN variants.
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 1,528 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 (BA). 33 distinct heterozygous ACAN variants were identified, including 19 novel variants. In the treatment group (n = 17), rhGH therapy lasted 4-61 months. Growth velocity (GV) at 3, 6, 9, 12, and 18 months was significantly higher than baseline (all P < 0.05). Changes in height standard deviation score (Ht SDS) at 18 and 24 months were significantly greater than those at 3 and 6 months (all P < 0.05). In the untreated group (n = 13), follow-up lasted 3-58 months, with final GV of 0-6.98 cm/year.
Conclusion:
Short stature and advanced BA 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.
