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 identified in a child with short stature, and rhGH therapy led to initial growth improvements, but further details on long-term outcomes are lacking.

Summary and findings

This case report describes a 7-year and 11-month-old Chinese girl with short stature, advanced bone age, and asymptomatic 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 emphasizes the importance of ACAN screening in children with unexplained short stature and related conditions.

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.

Limitations

Not reported in abstract.

Elsewhere in the HGH (Somatropin) corpus