Adult Height After Growth Hormone and Aromatase Inhibitor Therapy for Short Stature due to ACAN Mutation

Aggrecan (ACAN) deficiency is a cause of autosomal-dominant short stature, often accompanied by advanced bone age (BA) and early growth plate closure. Evidence for combined growth hormone (GH) plus aromatase inhibitor (AI) therapy in ACAN remains limited. Our objective is to report adult height in a child with a heterozygous ACAN variant who was treated with GH, followed by GH and AI during puberty.

A boy was first evaluated at 2 years and 6 months for short stature, had markedly advanced BA by 5 years and 6 months, and a novel heterozygous frameshift ACAN variant. GH therapy was started at 6 years of age for short stature and BA advancement with compromised predicted adult height (PAH). AI was added to GH therapy when he entered central puberty at 11 years of age. After 4.5 years of combined therapies with GH and AI, he attained an adult height of 156.3 cm, which is 9 cm below his mid-parental target height but 14 cm above his pretreatment PAH. No AI-related adverse effects were reported.

GH can improve growth velocity, and AIs may delay epiphyseal fusion by lowering estrogen conversion and thus extending the growth window. Our patient's height gain aligns with reported GH responses in ACAN and with data indicating that adjunctive AI can modestly increase PAH in boys with advanced BA.

This case highlights the potential benefits of combined GH and AI therapy in managing short stature in patients with ACAN mutation.