Association of Antenatal Evaluations with Postmortem and Genetic Findings in the Series of Fetal Osteogenesis Imperfecta

Abstract

<b><i>Introduction:</i></b> Counseling osteogenesis imperfecta (OI) pregnancies is challenging due to the wide range of onsets and clinical severities, from perinatal lethality to milder forms detected later in life. <b><i>Methods:</i></b> Thirty-eight individuals from 36 families were diagnosed with OI through prenatal ultrasonography and/or postmortem clinical and radiographic findings. Genetic analysis was conducted on 26 genes associated with OI in these subjects that emerged over the past 20 years; while some genes were examined progressively, all 26 genes were examined in the group where no pathogenic variations were detected. <b><i>Results:</i></b> Prenatal and postnatal observations both consistently showed short limbs in 97%, followed by bowing of the long bones in 89%. Among 32 evaluated cases, all exhibited cranial hypomineralization. Fractures were found in 29 (76%) cases, with multiple bones involved in 18 of them. Genetic associations were disclosed in 27 families with 22 (81%) autosomal dominant and five (19%) autosomal recessive forms, revealing 25 variants in six genes (<i>COL1A1</i>, <i>COL1A2</i>, <i>CREB3L1</i>, <i>P3H1</i>, <i>FKBP10</i>, and <i>IFITM5</i>), including nine novels. Postmortem radiological examination showed variability in intrafamily expression of <i>CREBL3-</i> and <i>P3H1</i>-related OI. <b><i>Conclusion:</i></b> Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetics, and postmortem evaluation.