Published January 1, 2024 | Version v1
Journal article Open

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

  • 1. Istanbul Univ, Istanbul Fac Med, Dept Med Genet, Istanbul, Turkiye
  • 2. Istanbul Univ, Istanbul Fac Med, Dept Obstet & Gynecol, Div Perinatol, Istanbul, Turkiye
  • 3. Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium
  • 4. Univ Med Ctr Gottingen, Inst Human Genet, Gottingen, Germany
  • 5. Istanbul Univ Cerrahpasa, Med Sch, Dept Pediat Genet, Istanbul, Turkiye

Description

Introduction: 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. Methods: 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. Results: 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 (COL1A1, COL1A2, CREB3L1, P3H1, FKBP10, and IFITM5), including nine novels. Postmortem radiological examination showed variability in intrafamily expression of CREBL3- and P3H1-related OI. Conclusion: Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetics, and postmortem evaluation.

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