Objectives: Achondroplasia is the most common form of skeletal dysplasia and is usually suspected in the third trimester of pregnancy based on abnormal sonographic findings. Non-invasive prenatal diagnosis (NIPD), based on the detection of pathogenic FGFR3 variants in maternal plasma, provides an accurate genetic confirmation. The aim of this study was to identify the sonographic markers most strongly associated with achondroplasia, with the intention of enhancing the specificity of NIPD referrals and improving diagnostic efficiency, thereby supporting clinicians in their diagnostic approach.
Methods: A retrospective cohort study was conducted on 275 NIPD tests performed in the laboratory between 2017 and 2023. Of these, 176 were requested due to sonographic abnormalities suggestive of achondroplasia. Sonographic reports were systematically reviewed to identify key ultrasound features correlated with a positive NIPD result.
Results: Among the NIPD tests ordered due to sonographic anomalies, 34.1% were confirmed positive for achondroplasia. Abnormal proximal end of the femur, frontal bossing, and a pronounced nasal saddle were the most specific markers, achieving a diagnostic yield of 87.5% when all three features were present. In contrast, short femur length alone had a poor diagnostic yield (8.9%).
Conclusion: Targeted sonographic phenotyping significantly improves the diagnostic yield of NIPD for achondroplasia. These findings support the need for more refined prenatal screening guidelines to enhance test specificity and optimise patient care as new achondroplasia treatments emerge.