The role of sonographic phenotyping in delivering an efficient non-invasive prenatal diagnosis (NIPD) service for FGFR3-related skeletal dysplasias.

OBJECTIVES: To evaluate the diagnostic yield of non-invasive prenatal diagnosis (NIPD) for FGFR3-related skeletal dysplasias and assess the accuracy of referrals based on sonographic findings to inform guidelines for referral. METHODS: We retrospectively reviewed laboratory and referral records from 2012-2018 to ascertain all NIPD tests performed using our next generation sequencing panel to detect FGFR3 mutations. We calculated the diagnostic yield of the test overall and when sub-divided according to the phenotypic features identified on ultrasound before testing. Pregnancy outcomes were ascertained wherever possible from referring centres. RESULTS: Of 335 tests, 261 were referred because of sonographic findings, of which 80 (31.3%) had a mutation. The diagnostic yield when short limbs were the only abnormal sonographic feature reported was 17.9% (30/168), increasing to 48.9% (23/47) in the presence of one, and 82.6% (19/23) in the presence of two or more characteristic features in addition to short limbs. CONCLUSIONS: Accurate sonographic phenotyping can maximise the diagnostic yield of NIPD in fetuses suspected to have FGFR3-related skeletal dysplasias. We suggest that clear guidelines for referral are necessary to increase benefits, decrease costs by preventing unnecessary NIPD, and potentially allow first-line broader spectrum testing for fetuses where the aetiology may be more heterogeneous. This article is protected by copyright. All rights reserved.