Phenotypic Characterization and rhGH Therapeutic Response in ACAN Children with Short Stature: A Real-World Study.
This study indicates that rhGH therapy may enhance growth in children with ACAN variants, but further research is needed to confirm these results and understand long-term effects.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the efficacy of recombinant human growth hormone (rhGH) therapy in 37 children with heterozygous ACAN variants identified among individuals with growth retardation. The treatment group consisted of 17 children who received rhGH therapy for 4-61 months. The study found significant increases in growth velocity and height standard deviation scores compared to baseline.
Abstract
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.
Background
This paper addresses the efficacy of rhGH therapy in children with short stature due to heterozygous ACAN variants. Prior knowledge indicates that ACAN variants are associated with growth retardation, but the specific therapeutic responses to rhGH in this population were not well characterized. Understanding the phenotypic features and treatment responses is important for guiding genetic screening and management strategies.
Methods
The study was a retrospective analysis of 37 children with heterozygous ACAN variants identified among 1,528 individuals with growth retardation at a pediatric medical center in China. The treatment group consisted of 17 children receiving rhGH therapy for 4-61 months. Primary outcomes included growth velocity and height standard deviation scores measured at various follow-up intervals.
Results
Among the 37 children, 78.4% had short stature and 75.7% had advanced bone age. Growth velocity at 3, 6, 9, 12, and 18 months was significantly higher than baseline (all P < 0.05). Height standard deviation scores at 18 and 24 months were significantly greater than at 3 and 6 months (all P < 0.05). In the untreated group, the final growth velocity ranged from 0 to 6.98 cm/year.
Interpretation
The findings suggest that rhGH therapy may promote growth in children with ACAN variants, but the clinical significance of the observed growth velocity increases should be interpreted cautiously given the small sample size and the retrospective nature of the study. The results align with existing literature on rhGH efficacy but highlight the need for controlled studies to confirm these findings and assess long-term outcomes.
Key findings
- 78.4% of children had short stature.
- 75.7% exhibited advanced bone age.
- Growth velocity at 3, 6, 9, 12, and 18 months was significantly higher than baseline (all P < 0.05).
- Changes in height standard deviation score at 18 and 24 months were significantly greater than those at 3 and 6 months (all P < 0.05).
- Final growth velocity in the untreated group was 0-6.98 cm/year.
Limitations
- Retrospective analysis with small sample size (n=37).
- Lacks a control group for comparison.
- Short follow-up duration for assessing long-term effects.
- Potential confounding factors not controlled for.