Research progress of short stature and advanced bone age, early-onset osteoarthritis and osteochondritis dissecans (SSOAOD) caused by acan gene mutation.

INTRODUCTION

Heterozygous mutations in the ACAN gene are a key genetic cause of non-syndromic familial short stature. The associated disease spectrum includes short stature, advanced bone age, early-onset osteoarthritis, and osteochondritis dissecans (SSOAOD). The clinical phenotype is highly heterogeneous, ranging from isolated short stature to severe skeletal developmental abnormalities, reflecting a continuous pathological process from growth plate dysfunction to premature joint degeneration.

METHODS

This summary synthesizes current clinical evidence and management approaches for ACAN-related short stature. Recombinant human growth hormone (rhGH) is the primary treatment used to improve height in affected children. Clinical management also integrates growth promotion, joint protection, genetic counseling, and screening of at-risk family members.

RESULTS

rhGH therapy provides moderate improvement in height, but its efficacy decreases with increasing age. Long-term safety of rhGH on joint health remains unclear. The disease spectrum illustrates progressive severity from short stature alone to significant skeletal and joint pathology.

DISCUSSION: Clinical care should adopt a multidisciplinary approach combining growth promotion, joint protection, and genetic counseling, including screening for at-risk family members. Future multicenter, long-term follow-up studies are needed to further clarify the molecular mechanisms of ACAN haploinsufficiency, assess the long-term articular effects of rhGH therapy, and establish early identification criteria, thereby providing a basis for developing targeted therapies.