Retrospective Study of Foramen Magnum Development in Patients with Achondroplasia Starting Vosoritide Before Age Three.

Abstract

Achondroplasia (ACH) is a monogenic skeletal dysplasia caused by gain-of-function variants in FGFR3, leading to impaired endochondral ossification and foramen magnum stenosis. Although vosoritide promotes endochondral ossification, its effects on foramen magnum development remain unclear. We evaluated the impact of early vosoritide administration on foramen magnum development in infants and young children with ACH using longitudinal magnetic resonance imaging (MRI). This retrospective single-center case series included nine patients who initiated vosoritide before age 3. Serial head MRI scans were analyzed. Anteroposterior and transverse diameters of the foramen magnum were measured and compared with reference curves from untreated ACH cohorts. Stenosis severity was assessed using the Achondroplasia Foramen Magnum Score (AFMS). Correlations between changes in body height standard deviation score (SDS) and foramen magnum dimensions were assessed. Vosoritide was initiated at a median age of 4 months, with a mean treatment duration of 2.5 years. Compared with untreated cohorts, steeper growth rates were observed in eight of nine patients for the anteroposterior and in all for the transverse diameter. Most remained at AFMS 1-2. One progressed to AFMS 3 and underwent decompression surgery at 11 months. No significant correlation was identified between changes in body height SDS and foramen magnum diameter. Early vosoritide administration may promote foramen magnum development in infants and young children with ACH, independent of systemic growth effects. Even when height improvement is limited, enhancement of foramen magnum growth may be clinically relevant.