A Novel ACAN Missense Variant in the G1 Domain Causes Short Stature, Advanced Bone Age, and Osteochondritis Dissecans: A Case Report and Literature Review.
A novel ACAN variant was found in a child with short stature, and growth hormone treatment led to initial catch-up growth, but further details on growth metrics were not provided.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This case report describes a 7-year and 11-month-old Chinese girl with short stature, advanced bone age, and knee osteochondritis dissecans. A novel heterozygous ACAN missense variant was identified, and recombinant human growth hormone was administered, resulting in early catch-up growth followed by reduced growth velocity. The study highlights the importance of ACAN screening in similar pediatric cases.
Abstract
Heterozygous ACAN variants are a major monogenic cause of short stature (SS). We reported a 7 years and 11 months Chinese girl with SS, advanced bone age (BA), and asymptomatic knee osteochondritis dissecans. Targeted next generation sequencing identified a novel paternally inherited heterozygous ACAN missense variant c.547G>C within the G1 domain, classified as likely pathogenic per ACMG standards. Recombinant human growth hormone (rhGH) induced robust early catch up growth followed by reduced growth velocity, and the patient remains under follow up. This case expands the aggrecanopathy variant spectrum and supports routine ACAN screening in children with unexplained SS, accelerated BA, and osteochondral lesions.
Background
This paper addresses the genetic basis of short stature, particularly focusing on ACAN variants as a monogenic cause. Prior knowledge indicated that ACAN mutations can lead to growth disorders, but specific variants and their clinical implications were less understood. This study is significant as it expands the known spectrum of ACAN variants and suggests routine screening for affected children.
Methods
This is a case report involving a 7-year and 11-month-old girl. Genetic analysis was performed using targeted next generation sequencing to identify ACAN variants. The primary outcome measured was the effect of recombinant human growth hormone on growth velocity.
Results
The identified ACAN variant was classified as likely pathogenic. The patient showed early catch up growth after treatment with recombinant human growth hormone, but specific growth metrics were not reported. No statistical analysis or p-values were provided in the abstract.
Interpretation
The findings contribute to the understanding of ACAN-related growth disorders, but the clinical significance of the identified variant remains uncertain without broader context or comparative data. The effect of recombinant human growth hormone, while noted as robust, lacks detailed metrics to assess clinical relevance. Limitations include the absence of long-term follow-up data and the single-case nature of the report.
Key findings
- Identified a novel paternally inherited heterozygous ACAN missense variant c.547G>C.
- Patient exhibited advanced bone age and asymptomatic knee osteochondritis dissecans.
- Recombinant human growth hormone induced robust early catch up growth followed by reduced growth velocity.
Limitations
- Single case report limits generalizability.
- No long-term follow-up data provided.
- Specific growth metrics post-treatment not detailed.
- Lack of statistical analysis in abstract.