Impact of Growth Hormone Treatment in Children From an Extended Family With ACAN -Related Short Stature.

Heterozygous variants in the ACAN gene are a recognized cause of short stature. We aimed to evaluate the response to growth hormone (GH) treatment in members of an extended family carrying an ACAN variant. Clinical and laboratory data of five related children were retrospectively collected. GH therapy was initiated at a mean age of 3.2 ± 2.1 years and treated for 6.4 ± 5.0 years. The height standard deviation scores (SDS) increased from -3.3 ± 1.0 to -2.0 ± 1.1 (p = 0.001), with a mean gain of 1.3 ± 0.3 SDS. The most notable increase in growth velocity SDS occurred during the first year of treatment (-0.5 ± 0.6 to 2.1 ± 1.2; p = 0.04). No adverse effects were observed, and bone age did not advance significantly. Three children entered puberty between the ages of 10 and 11.6 years and received adjunctive gonadotropin releasing hormone analog therapy. Genetic testing identified a heterozygous nonsense variant in the ACAN (c.2023C>T; p.Arg675*). Our findings suggest that GH therapy can improve growth velocity in children with ACAN-related short stature, though the degree of response varies even within the same family. The long-term impact on final adult height remains to be elucidated.