Molecular autopsy for fetal structural anomaly: diagnostic and clinical utility of multidisciplinary team approach

E. Wall, E. Petley, F. Mone, S. Doyle, L. Hartles-Spencer, S. K. Allen, J. Castleman, T. Marton, D. Williams

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Abstract

Objectives: In the West Midlands Regional Genetic Service, cases of perinatal death with a possible genetic diagnosis are evaluated by the Perinatal Pathology Genetic Multidisciplinary Team (MDT). The MDT assessed autopsy findings and considered genomic assessments. The objective of this retrospective service evaluation was to determine the clinical utility of the MDT. This is the first evaluation since the introduction of whole genome and whole exome sequencing in routine clinical care.
Method: The outcomes for all the perinatal MDT cases from January 2021 to December 2021 were examined. All cases received a full or partial post-mortem examination (PM) and a chromosomal microarray. Demographics, phenotype, MDT recommendations, genetic testing, diagnoses, outcomes, impact of PM and impact of genetic testing were collected from patient case notes.
Results: One hundred and twenty-three cases were discussed at the MDT meeting in 2021. Genetic evaluation was recommended in 84 cases and accepted in 64 cases. A range of genetic tests were requested according to indication and availability. Thirty diagnoses were identified in 29 cases from 26 unrelated families. The diagnostic yield was 24% (29/123) of all cases or 45% (29/64) of the cases with a suspected genetic diagnosis who underwent genetic testing. PM examination added clinically actionable phenotype data in 79% of cases. A genetic diagnosis enabled accurate counselling of recurrence risk and provision of appropriate follow-up, including prenatal testing and preimplantation diagnosis for patients with inherited conditions.
Conclusions: Genomic testing was a clinically useful addition to (but not a substitute for) PM examination in perinatal cases associated with structural anomalies. The MDT model helped assess cases and plan appropriate follow-up. Expedited whole genome sequencing or panel-agnostic analysis were most appropriate for heterogeneous presentations. This broad approach can also expand prenatal phenotypes and detect novel disease genes and should be a priority for future research.
Original languageEnglish
JournalUltrasound in Obstetrics & Gynecology
Early online date22 Mar 2024
DOIs
Publication statusEarly online date - 22 Mar 2024

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Keywords

  • molecular post‐mortem
  • perinatal post‐mortem
  • prenatal exome sequencing
  • service evaluation
  • whole genome sequencing

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