short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans is a rare genetic skeletal disorder that primarily affects the development of cartilage and bone. It is related to pathogenic variants in the ACAN gene, which disrupt the normal function of aggrecan, an essential component of cartilage. The condition typically presents in late childhood or adolescence, with affected individuals often exhibiting disproportionate short stature and joint abnormalities. Currently, precise prevalence estimates are not available, and the disorder is considered to be very rare.

The clinical features include consistently accelerated skeletal maturation, which is observed in all affected individuals, and a high frequency of short stature. Additional features that may be present include mandibular prognathia, midface retrusion, short thumb, brachydactyly, and a depressed nasal bridge. In a smaller subset of patients, osteochondritis dissecans and premature osteoarthritis have been reported. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the ACAN gene, which plays a critical role in the production of aggrecan, a fundamental protein in cartilage structure. It is inherited in an autosomal dominant pattern, meaning that a mutation in only one of the two copies of the gene is sufficient to cause the disorder. Within affected families, the expression of symptoms can differ widely, highlighting variable expressivity. Genetic counseling is recommended to help families understand the inheritance implications and to guide decisions related to family planning.

Currently, management focuses on supportive care and symptom management since there are no treatments specifically approved for this condition. A multidisciplinary approach, including orthopedic evaluation and physical therapy, is important to help manage joint pain, mobility issues, and other related complications. Regular surveillance is an essential part of long-term care, ensuring that any emerging complications are identified and addressed promptly. Patients and families should discuss treatment options with their healthcare team, and genetic counseling is advised to better understand the implications of the autosomal dominant inheritance.

Outcomes for individuals with this condition vary widely, with some experiencing more pronounced skeletal and joint issues while others have a milder clinical course. Modern advancements in supportive care have contributed to improvements in quality of life, although the overall progression remains unpredictable. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling for guidance on long-term management.

Clinical trials are currently underway exploring new treatment approaches for this condition, reflecting an active area of research. Individuals interested in learning about clinical trial opportunities can search ClinicalTrials.gov or consult their care team regarding eligibility. Ongoing research efforts aim to further understand the molecular mechanisms and to potentially develop targeted therapies in the future.