Clinical and genetic profile of achondroplasia: a descriptive study from a tertiary care center in Saudi Arabia

Achondroplasia (ACH) results from a missense mutation in the FGFR3 (fibroblast growth factor receptor 3) gene, representing the primary cause of short stature in humans. This study aims to describe the clinical features, complications, and management outcomes of Saudi patients with achondroplasia.

This retrospective study included achondroplasia cases followed at the endocrinology clinic at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, from (2015-2025).

Thirty-three patients were included; 32 were heterozygous and one was homozygous for the FGFR3 c.1138G > A variant. Median age at presentation was 24 months (IQR 7-60), and 54.5% were male. Short stature was universal, with frontal bossing and skeletal deformities present in 93.9%. Developmental delay was observed in 54.5%, while neurological symptoms and hearing loss were each noted in 42.4%. Clinical suspicion of obstructive sleep apnea (OSA) was identified in 17/33 patients (51.5%), with 41.2% (7/17) requiring surgical intervention. Yet, polysomnography was performed in only 10 patients and confirmed OSA in all cases. Radiologic abnormalities were common, with abnormal brain or spine imaging in 96.4% (27/28), foramen magnum stenosis in 50% (14/28), and spinal abnormalities in 71.4% (20/28). Median baseline height SDS was - 5.5. Growth hormone therapy was used in four patients, with only one demonstrating transient benefit. Overall mortality was 9.1% (3/33), including one homozygous infant and two heterozygous patients.

This study provides the largest single-center characterization of achondroplasia in Saudi Arabia. The findings highlight the high burden of airway and hearing complications and the limited long-term efficacy of GH therapy, underscoring the need for multidisciplinary and targeted management strategies.